Thu, 21 Aug 2008 01:22:18 BST CiteULike: hplatero's library [542 articles] http://www.citeulike.org/user/hplatero CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/user/hplatero/article/3019524 <i>Genes Dev., Vol. 18, No. 22. (15 November 2004), pp. 2785-2797.</i><br /><br />The possibility that single-cell organisms undergo programmed cell death has been questioned in part because they lack several key components of the mammalian cell death machinery. However, yeast encode a homolog of human Drp1, a mitochondrial fission protein that was shown previously to promote mammalian cell death and the excessive mitochondrial fragmentation characteristic of apoptotic mammalian cells. In support of a primordial origin of programmed cell death involving mitochondria, we found that the Saccharomyces cerevisiae homolog of human Drp1, Dnm1, promotes mitochondrial fragmentation/degradation and cell death following treatment with several death stimuli. Two Dnm1-interacting factors also regulate yeast cell death. The WD40 repeat protein Mdv1/Net2 promotes cell death, consistent with its role in mitochondrial fission. In contrast to its fission function in healthy cells, Fis1 unexpectedly inhibits Dnm1-mediated mitochondrial fission and cysteine protease-dependent cell death in yeast. Furthermore, the ability of yeast Fis1 to inhibit mitochondrial fission and cell death can be functionally replaced by human Bcl-2 and Bcl-xL. Together, these findings indicate that yeast and mammalian cells have a conserved programmed death pathway regulated by a common molecular component, Drp1/Dnm1, that is inhibited by a Bcl-2-like function. 10.1101/gad.1247904 Mitochondrial fission proteins regulate programmed cell death in yeast Yihru Fannjiang Wen-Chih Cheng Sarah Lee Bing Qi Jonathan Pevsner Michael Mccaffery Blake Hill Gorka Basanez Marie Hardwick doi:10.1101/gad.1247904 Genes Dev., Vol. 18, No. 22. (15 November 2004), pp. 2785-2797. 2008-07-18T19:50:51-00:00 2004 Genes Dev. 18 22 2785 2797 apoptosis cit1 http://www.citeulike.org/user/hplatero/article/2919903 <i>J. Cell Biol., Vol. 151, No. 4. (13 November 2000), pp. 763-778.</i><br /><br />Members of the protein kinase C (PKC) family of signal transduction molecules have been widely implicated in regulation of cell growth and differentiation, although the underlying molecular mechanisms involved remain poorly defined. Using combined in vitro and in vivo intestinal epithelial model systems, we demonstrate that PKC signaling can trigger a coordinated program of molecular events leading to cell cycle withdrawal into G0. PKC activation in the IEC-18 intestinal crypt cell line resulted in rapid downregulation of D-type cyclins and differential induction of p21waf1/cip1 and p27kip1, thus targeting all of the major G1/S cyclin-dependent kinase complexes. These events were associated with coordinated alterations in expression and phosphorylation of the pocket proteins p107, pRb, and p130 that drive cells to exit the cell cycle into G0 as indicated by concomitant downregulation of the DNA licensing factor cdc6. Manipulation of PKC isozyme levels in IEC-18 cells demonstrated that PKCalpha alone can trigger hallmark events of cell cycle withdrawal in intestinal epithelial cells. Notably, analysis of the developmental control of cell cycle regulatory molecules along the crypt-villus axis revealed that PKCalpha activation is appropriately positioned within intestinal crypts to trigger this program of cell cycle exit-specific events in situ. Together, these data point to PKCalpha as a key regulator of cell cycle withdrawal in the intestinal epithelium. 10.1083/jcb.151.4.763 Protein Kinase C Signaling Mediates a Program of Cell Cycle Withdrawal in the Intestinal Epithelium Mark Frey Jennifer Clark Olga Leontieva Joshua Uronis Adrian Black Jennifer Black doi:10.1083/jcb.151.4.763 J. Cell Biol., Vol. 151, No. 4. (13 November 2000), pp. 763-778. 2008-06-23T23:56:16-00:00 2000 J. Cell Biol. 151 4 763 778 g0 http://www.citeulike.org/user/hplatero/article/2919517 <i>Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Vol. 1783, No. 7. (July 2008), pp. 1320-1327.</i><br /><br />Damaging environment, certain intracellular defects or heterologous expression of pro-apoptotic genes induce death in yeast cells exhibiting typical markers of apoptosis. In mammals, apoptosis can be directed by the activation of groups of proteases, called caspases, that cleave specific substrates and trigger cell death. In addition, in plants, fungi, Dictyostelium and metazoa, paracaspases and metacaspases have been identified that share some homologies with caspases but showing different substrate specificity. In the yeast Saccharomyces cerevisiae, a gene (MCA1/YCA1) has been identified coding for a metacaspase involved in the induction of cell death. Metacaspases are not biochemical, but sequence and functional homologes of caspases, as deletion of them rescues entirely different death scenarios. In this review we will summarize the current knowledge in S. cerevisiae on apoptotic processes, induced by internal and external triggers, which are dependent on the metacaspase gene YCA1. Caspase-dependent apoptosis in yeast Cristina Mazzoni Claudio Falcone doi:10.1016/j.bbamcr.2008.02.015 Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Vol. 1783, No. 7. (July 2008), pp. 1320-1327. 2008-06-23T18:01:19-00:00 2008 Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1783 7 1320 1327 apoptosis yca1 http://www.citeulike.org/user/hplatero/article/393112 <i>Nature, Vol. 425, No. 6959. (16 October 2003), pp. 686-691.</i><br /><br />A fundamental goal of cell biology is to define the functions of proteins in the context of compartments that organize them in the cellular environment. Here we describe the construction and analysis of a collection of yeast strains expressing full-length, chromosomally tagged green fluorescent protein fusion proteins. We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories, and provide localization information for 70% of previously unlocalized proteins. Analysis of this high-resolution, high-coverage localization data set in the context of transcriptional, genetic, and protein-protein interaction data helps reveal the logic of transcriptional co-regulation, and provides a comprehensive view of interactions within and between organelles in eukaryotic cells. Global analysis of protein localization in budding yeast. WK Huh JV Falvo LC Gerke AS Carroll RW Howson JS Weissman EK O'Shea doi:10.1038/nature02026 Nature, Vol. 425, No. 6959. (16 October 2003), pp. 686-691. 2005-11-15T06:04:50-00:00 2003 Nature 1476-4687 425 6959 686 691 gfp http://www.citeulike.org/user/hplatero/article/560813 <i>Nature (22 March 2006)</i> Global landscape of protein complexes in the yeast Saccharomyces cerevisiae Nevan Krogan Gerard Cagney Haiyuan Yu Gouqing Zhong Xinghua Guo Alexandr Ignatchenko Joyce Li Shuye Pu Nira Datta Aaron Tikuisis Thanuja Punna Josã© Peregrã­n-Alvarez Michael Shales Xin Zhang Michael Davey Mark Robinson Alberto Paccanaro James Bray Anthony Sheung Bryan Beattie Dawn Richards Veronica Canadien Atanas Lalev Frank Mena Peter Wong Andrei Starostine Myra Canete James Vlasblom Samuel Wu Chris Orsi Sean Collins Shamanta Chandran Robin Haw Jennifer Rilstone Kiran Gandi Natalie Thompson Gabe Musso Peter St Onge Shaun Ghanny Mandy Lam Gareth Butland Amin Altaf-Ul Shigehiko Kanaya Ali Shilatifard Erin O'Shea Jonathan Weissman James Ingles Timothy Hughes John Parkinson Mark Gerstein Shoshana Wodak Andrew Emili Jack Greenblatt doi:10.1038/nature04670 Nature (22 March 2006) 2006-03-23T02:32:52-00:00 2006 Nature 0028-0836 Nature Publishing Group gfp http://www.citeulike.org/user/hplatero/article/2909032 <i>Mechanisms of Ageing and Development, Vol. 127, No. 9. (September 2006), pp. 733-740.</i><br /><br />Only recently have the studies of yeast ageing started to focus on the S288c-derived strains used extensively in genomics and on the longest lifespans. Chronological longevity (stationary (G0) survival) of such strains is greater when cells are pre-grown on a respiratory carbon source, as compared to when they are pre-grown on glucose (the latter a respiration-repressing sugar). Prior adaptation to efficient respiratory maintenance also ensures that such chronologically aged yeast cells still display a full replicative lifespan should they reenter the cell cycle. In contrast, cells that are pre-grown on glucose exhibit marked and progressive losses of replicative potential as they age chronologically in stationary phase. Increasing the respiratory activity in glucose-grown cultures by HAP4 gene overexpression increased survival and reversed the loss of replicative potential during a subsequent stationary phase. Adaptation to efficient respiratory maintenance is therefore important, not just for maximal longevity, but also for the maintenance of a full replicative lifespan by chronologically ageing cultures of yeast. In such respiration-adapted cultures, losses of the Sch9 protein kinase or Yca1 caspase both shortened lifespan. In contrast loss of Yap1, the major transcriptional regulator of the oxidative stress response, generated a small increase in chronological lifespan in certain strain backgrounds. It would appear, therefore, that any induction of oxidative stress response genes in chronologically ageing yeast is not operating to generate an increase in longevity, even though such protective effects might be expected from the increased proxidant status of these cells over time. Preadaptation to efficient respiratory maintenance is essential both for maximal longevity and the retention of replicative potential in chronologically ageing yeast Peter Piper Nicholas Harris Morag Maclean doi:10.1016/j.mad.2006.05.004 Mechanisms of Ageing and Development, Vol. 127, No. 9. (September 2006), pp. 733-740. 2008-06-19T22:57:38-00:00 2006 Mechanisms of Ageing and Development 127 9 733 740 cit1 g0 http://www.citeulike.org/user/hplatero/article/814671 <i>FEBS Lett, Vol. 580, No. 12. (22 May 2006), pp. 2821-2829.</i><br /><br />The target of rapamycin (TOR) is an ancient effector of cell growth that integrates signals from growth factors and nutrients. Two downstream effectors of mammalian TOR, the translational components S6K1 and 4EBP1, are commonly used as reporters of mTOR activity. The conical signaling cascade initiated by growth factors is mediated by PI3K, PKB, TSC1/2 and Rheb. However, the process through which nutrients, i.e., amino acids, activate mTOR remains largely unknown. Evidence exists for both an intracellular and/or a membrane bound sensor for amino acid mediated mTOR activation. Research in eukaryotic models, has implicated amino acid transporters as nutrient sensors. This review describes recent advances in nutrient signaling that impinge on mTOR and its targets including hVps34, class III PI3K, a transducer of nutrient availability to mTOR. The amino acid sensitive TOR pathway from yeast to mammals. SG Dann G Thomas doi:10.1016/j.febslet.2006.04.068 FEBS Lett, Vol. 580, No. 12. (22 May 2006), pp. 2821-2829. 2006-08-23T22:40:08-00:00 2006 FEBS Lett 0014-5793 580 12 2821 2829 cit1 http://www.citeulike.org/user/hplatero/article/2909023 <i>Russian Journal of Genetics, Vol. 39, No. 6. (1 June 2003), pp. 604-609.</i><br /><br />The Krebs cycle is one of the major metabolic pathways in a cell, which includes both catabolic and anabolic reactions. The first enzyme of the Krebs cycle, citrate synthase, catalyzes one of a few irreversible reactions of the cycle, citrate formation from acetyl-CoA and oxaloacetate. Expression of the CIT1 gene encoding the mitochondrial form of this enzyme inSaccharomyces cerevisiae is repressed on glucose- and glutamate-containing medium and activated on the raffinose-containing medium. In this work, the dependence of glucose repression of the CIT1 gene on the content of phosphate in the medium was studied. On the phosphate-deficient medium, the level of the CIT1 gene expression was increased twice. A low-molecular-weight (about 34 kDa) protein was identified and shown to interact with a region of the CIT1gene promoter (from –367 to –348 bp), which controls the glucose repression. The results obtained suggest that the Pho4 protein is involved in regulation of the CIT1gene expression on the glucose-containing and phosphate-deficient medium. Disruption of the PHO85 gene encoding phosphoprotein kinase (Pho4p is the substrate of this enzyme) leads to alleviation of glucose repression of the CIT1 gene. Thus, in yeast cells grown in the presence of glucose, the PHO85gene mediates downregulation of theCIT1expression. Effect of the pho85 Mutation on Catabolite Repression of the CIT1 Gene in Yeasts Saccharomyces cerevisiae MV Padkina SA Tarasov SL Karsten LV Parfenova Yu Popova EV Sambuk doi:10.1023/A:1024489322873 Russian Journal of Genetics, Vol. 39, No. 6. (1 June 2003), pp. 604-609. 2008-06-19T22:44:06-00:00 2003 Russian Journal of Genetics 39 6 604 609 cit1 http://www.citeulike.org/user/hplatero/article/2908889 <i>Nucleic acids research, Vol. 35, No. 22. (2007), pp. 7514-7526.</i><br /><br />Yeast mother cell-specific ageing is characterized by a limited capacity to produce daughter cells. The replicative lifespan is determined by the number of cell cycles a mother cell has undergone, not by calendar time, and in a population of cells its distribution follows the Gompertz law. Daughter cells reset their clock to zero and enjoy the full lifespan characteristic for the strain. This kind of replicative ageing of a cell population based on asymmetric cell divisions is investigated as a model for the ageing of a stem cell population in higher organisms. The simple fact that the daughter cells can reset their clock to zero precludes the accumulation of chromosomal mutations as the cause of ageing, because semiconservative replication would lead to the same mutations in the daughters. However, nature is more complicated than that because, (i) the very last daughters of old mothers do not reset the clock; and (ii) mutations in mitochondrial DNA could play a role in ageing due to the large copy number in the cell and a possible asymmetric distribution of damaged mitochondrial DNA between mother and daughter cell. Investigation of the loss of heterozygosity in diploid cells at the end of their mother cell-specific lifespan has shown that genomic rearrangements do occur in old mother cells. However, it is not clear if this kind of genomic instability is causative for the ageing process. Damaged material other than DNA, for instance misfolded, oxidized or otherwise damaged proteins, seem to play a major role in ageing, depending on the balance between production and removal through various repair processes, for instance several kinds of proteolysis and autophagy. We are reviewing here the evidence for genetic change and its causality in the mother cell-specific ageing process of yeast. Yeast mother cell-specific ageing, genetic (in)stability, and the somatic mutation theory of ageing. P Laun CV Bruschi JR Dickinson M Rinnerthaler G Heeren R Schwimbersky R Rid M Breitenbach Nucleic acids research, Vol. 35, No. 22. (2007), pp. 7514-7526. 2008-06-19T21:30:42-00:00 2007 Nucleic acids research 1362-4962 35 22 7514 7526 apoptosis http://www.citeulike.org/user/hplatero/article/2851068 <i>Yeast, Vol. 24 (2007), pp. 145-154.</i> Global protein expression profiling of budding yeast in response to DNA damage Min-Woo Eun-Jung Yeast, Vol. 24 (2007), pp. 145-154. 2008-05-30T21:31:59-00:00 2007 Yeast 24 145 154 dna_damage http://www.citeulike.org/user/hplatero/article/2851058 <i>TRENDS in Biochemical Science, Vol. 30, No. 5. (May 2005)</i> Mediator comes of age Roger Kornberg TRENDS in Biochemical Science, Vol. 30, No. 5. (May 2005) 2008-05-30T21:24:05-00:00 2005 TRENDS in Biochemical Science 30 5 mediator http://www.citeulike.org/user/hplatero/article/2851050 <i>Oncogene, Vol. 20, No. 19. (April 2001), pp. 2438-2452.</i> Close encounters of many kinds: Fos-Jun interactions that mediate transcription regulatory specificity Yurii Oncogene, Vol. 20, No. 19. (April 2001), pp. 2438-2452. 2008-05-30T21:20:39-00:00 2001 Oncogene 20 19 2438 2452 bzip http://www.citeulike.org/user/hplatero/article/2845991 <i>Proceedings of the National Academy of Sciences of the United States of America, Vol. 96, No. 26. (21 December 1999), pp. 14866-14870.</i><br /><br />The immunosuppressant rapamycin inhibits Tor1p and Tor2p (target of rapamycin proteins), ultimately resulting in cellular responses characteristic of nutrient deprivation through a mechanism involving translational arrest. We measured the immediate transcriptional response of yeast grown in rich media and treated with rapamycin to investigate the direct effects of Tor proteins on nutrient-sensitive signaling pathways. The results suggest that Tor proteins directly modulate the glucose activation and nitrogen discrimination pathways and the pathways that respond to the diauxic shift (including glycolysis and the citric acid cycle). Tor proteins do not directly modulate the general amino acid control, nitrogen starvation, or sporulation (in diploid cells) pathways. Poor nitrogen quality activates the nitrogen discrimination pathway, which is controlled by the complex of the transcriptional repressor Ure2p and activator Gln3p. Inhibiting Tor proteins with rapamycin increases the electrophoretic mobility of Ure2p. The work presented here illustrates the coordinated use of genome-based and biochemical approaches to delineate a cellular pathway modulated by the protein target of a small molecule. Rapamycin-modulated transcription defines the subset of nutrient-sensitive signaling pathways directly controlled by the Tor proteins. JS Hardwick FG Kuruvilla JK Tong AF Shamji SL Schreiber Proceedings of the National Academy of Sciences of the United States of America, Vol. 96, No. 26. (21 December 1999), pp. 14866-14870. 2008-05-29T22:48:42-00:00 1999 Proceedings of the National Academy of Sciences of the United States of America 0027-8424 96 26 14866 14870 rap http://www.citeulike.org/user/hplatero/article/2019981 <i>Mol Biol Cell, Vol. 15, No. 3. (March 2004), pp. 1297-1312.</i><br /><br />To help define the pathologies associated with yeast cells as they age, we analyzed the transcriptome of young and old cells isolated by elutriation, which allows isolation of biochemical quantities of old cells much further advanced in their life span than old cells prepared by the biotin-streptavidin method. Both 18-generation-old wild-type yeast and 8-generation-old cells from a prematurely aging mutant (dna2-1), with a defect in DNA replication, were evaluated. Genes involved in gluconeogenesis, the glyoxylate cycle, lipid metabolism, and glycogen production are induced in old cells, signifying a shift toward energy storage. We observed a much more extensive generalized stress response known as the environmental stress response (ESR), than observed previously in biotin-streptavidin-isolated cells, perhaps because the elutriated cells were further advanced in their life span. In addition, there was induction of DNA repair genes that fall in the so-called DNA damage "signature" set. In the dna2-1 mutant, energy production genes were also induced. The response in the dna2-1 strain is similar to the telomerase delete response, genes whose expression changes during cellular senescence in telomerase-deficient cells. We propose that these results suggest, albeit indirectly, that old cells are responding to genome instability. The transcriptome of prematurely aging yeast cells is similar to that of telomerase-deficient cells. I Lesur JL Campbell doi:10.1091/mbc.E03-10-0742 Mol Biol Cell, Vol. 15, No. 3. (March 2004), pp. 1297-1312. 2007-11-29T22:46:09-00:00 2004 Mol Biol Cell 1059-1524 15 3 1297 1312 acs1 cit1 http://www.citeulike.org/user/hplatero/article/2842914 <i>Mol. Biol. Cell, Vol. 13, No. 11. (1 November 2002), pp. 3901-3914.</i><br /><br />On solid substrate, growing yeast colonies alternately acidify and alkalinize the medium. Using morphological, cytochemical, genetic, and DNA microarray approaches, we characterized six temporal steps in the "acid-to-alkali" colony transition. This transition is connected with the production of volatile ammonia acting as starvation signal between colonies. We present evidence that the three membrane proteins Ato1p, Ato2p, and Ato3p, members of the YaaH family, are involved in ammonia production in Saccharomyces cerevisiae colonies. The acid-to-alkali transition is connected with decrease of mitochondrial oxidative catabolism and by peroxisome activation, which in parallel with activation of biosynthetic pathways contribute to decrease the general stress level in colonies. These metabolic features characterize a novel survival strategy used by yeast under starvation conditions prevalent in nature. 10.1091/mbc.E01-12-0149 Ammonia Pulses and Metabolic Oscillations Guide Yeast Colony Development Zdena Palkova Frederic Devaux Marketa Ricicova Lucie Minarikova Stephane Le Crom Claude Jacq doi:10.1091/mbc.E01-12-0149 Mol. Biol. Cell, Vol. 13, No. 11. (1 November 2002), pp. 3901-3914. 2008-05-28T23:43:24-00:00 2002 Mol. Biol. Cell 13 11 3901 3914 acs1 http://www.citeulike.org/user/hplatero/article/2828864 <i>Mol. Cell. Biol., Vol. 18, No. 8. (1 August 1998), pp. 4463-4470.</i><br /><br />The macrolide antibiotic rapamycin inhibits cellular proliferation by interfering with the highly conserved TOR (for target of rapamycin) signaling pathway. Growth arrest of budding yeast cells treated with rapamycin is followed by the program of molecular events that characterizes entry into G0 (stationary phase), including the induction of polymerase (Pol) II genes typically expressed only in G0. Normally, progression into G0 is characterized by transcriptional repression of the Pol I and III genes. Here, we show that rapamycin treatment also causes the transcriptional repression of Pol I and III genes. The down-regulation of Pol III transcription is TOR dependent. While it coincides with translational repression by rapamycin, transcriptional repression is due in part to a translation-independent effect that is evident in extracts from a conditional tor2 mutant. Biochemical experiments reveal that RNA Pol III and probably transcription initiation factor TFIIIB are targets of repression by rapamycin. In view of previous evidence that TFIIIB and Pol III are inhibited when protein phosphatase 2A (PP2A) function is impaired, and that PP2A is a component of the TOR pathway, our results suggest that TOR signaling regulates Pol I and Pol III transcription in response to nutrient growth signals. Rapamycin Induces the G0 Program of Transcriptional Repression in Yeast by Interfering with the TOR Signaling Pathway Dean Zaragoza Ataollah Ghavidel Joseph Heitman Michael Schultz Mol. Cell. Biol., Vol. 18, No. 8. (1 August 1998), pp. 4463-4470. 2008-05-25T03:50:00-00:00 1998 Mol. Cell. Biol. 18 8 4463 4470 tor_signaling http://www.citeulike.org/user/hplatero/article/2828232 <i>Biochimica et biophysica acta (4 March 2008)</i><br /><br />It is our intention to give the reader a short overview of the relationship between apoptosis and senescence in yeast mother cell-specific aging. We are studying yeast as an aging model because we want to learn something of the basic biology of senescence and apoptosis even from a unicellular eukaryotic model system, using its unrivalled ease of genetic analysis. Consequently, we will discuss also some aspects of apoptosis in metazoa and the relevance of yeast apoptosis and aging research for cellular (Hayflick type) and organismic aging of multicellular higher organisms. In particular, we will discuss the occurrence and relevance of apoptotic phenotypes for the aging process. We want to ask the question whether apoptosis (or parts of the apoptotic process) are a possible cause of aging or vice versa and want to investigate the role of the cellular stress response system in both of these processes. Studying the current literature, it appears that little is known for sure in this field and our review will therefore be, for a large part, more like a memorandum or a program for future research. Senescence and apoptosis in yeast mother cell-specific aging and in higher cells: A short review. Peter Laun Gino Heeren Mark Rinnerthaler Raphaela Rid Sonja Kössler Lore Koller Michael Breitenbach doi:10.1016/j.bbamcr.2008.02.008 Biochimica et biophysica acta (4 March 2008) 2008-05-24T21:30:23-00:00 2008 Biochimica et biophysica acta 0006-3002 apoptosis http://www.citeulike.org/user/hplatero/article/2821422 <i>Seminars in Cancer Biology, Vol. 17, No. 2. (April 2007), pp. 112-121.</i><br /><br />Yeast are eukaryotic unicellular organisms that are easy to cultivate and offer a wide spectrum of genetic and cytological tools for research. Yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe have successfully been used as models for human cell division cycle. Stress conditions, cellular ageing, failed mating, certain mutations or heterologous expression of proapoptotic genes induce yeast cell death with the characteristic markers of apoptosis. Several crucial regulators of apoptosis are conserved between metazoans and yeast. This simple model organism offers the possibility to identify conserved and new components of the apoptotic machinery and to elucidate the regulatory pathways beyond. Yeast apoptosis--From genes to pathways Kai-Uwe Fröhlich Heike Fussi Christoph Ruckenstuhl doi:10.1016/j.semcancer.2006.11.006 Seminars in Cancer Biology, Vol. 17, No. 2. (April 2007), pp. 112-121. 2008-05-21T21:49:51-00:00 2007 Seminars in Cancer Biology 17 2 112 121 apoptosis http://www.citeulike.org/user/hplatero/article/383060 <i>Trends Cell Biol (12 October 2005)</i><br /><br />The release of reactive oxygen species (ROS) by mitochondria instigates the pathways of programmed cell death in eukaryotic cells. Gourlay and Ayscough present intriguing experimental evidence that mutations in the genes encoding the regulatory proteins End3p and Sla1p, which influence actin dynamics in budding yeast, lead to a loss of mitochondrial membrane potential, resulting in ROS production and apoptosis. This effect can be suppressed by downregulation of the RAS-cAMP signaling pathway, thus establishing the existence of a new and complex regulatory network. The actin cytoskeleton, RAS-cAMP signaling and mitochondrial ROS in yeast apoptosis. Michael Breitenbach Peter Laun Mario Gimona doi:10.1016/j.tcb.2005.09.011 Trends Cell Biol (12 October 2005) 2005-11-07T21:47:22-00:00 2005 Trends Cell Biol 0962-8924 apoptosis http://www.citeulike.org/user/hplatero/article/2817853 <i>Proceedings of the National Academy of Sciences, Vol. 96, No. 18. (31 August 1999), pp. 10170-10175.</i><br /><br />10.1073/pnas.96.18.10170 Role for yeast inhibitor of apoptosis (IAP)-like proteins in cell division Anthony Uren Traude Beilharz Matthew O'Connell Sarah Bugg Rosemary van Driel David Vaux Trevor Lithgow doi:10.1073/pnas.96.18.10170 Proceedings of the National Academy of Sciences, Vol. 96, No. 18. (31 August 1999), pp. 10170-10175. 2008-05-20T21:46:39-00:00 1999 Proceedings of the National Academy of Sciences 96 18 10170 10175 apoptosis http://www.citeulike.org/user/hplatero/article/2817800 <i>J Cell Sci, Vol. 119, No. 9. (1 May 2006), pp. 1843-1851.</i><br /><br />Inhibitor-of-apoptosis proteins (IAPs) play a crucial role in the regulation of metazoan apoptosis. IAPs are typically characterized by the presence of one to three baculovirus IAP repeat (BIR) domains that are essential for their anti-apoptotic activity. Bir1p is the sole BIR-protein in yeast and has been shown to participate in chromosome segregation events. Here, we show that Bir1p is a substrate for Nma111p, which is the homologue of the human pro-apoptotic serine protease Omi/HtrA2 and which is known to mediate apoptosis in yeast. Bir1p is a cytoplasmic and nuclear protein, and yeast cells lacking bir1 are more sensitive to apoptosis induced by oxidative stress. Consistently, overexpression of Bir1p reduces apoptosis-like cell death, whereas this protective effect can be antagonized in vivo by simultaneous overexpression of Nma111p. Moreover, chronologically aged cells that constitutively overexpress Bir1p show a delayed onset of cell death. Therefore, Bir1p, like its closest metazoan homologues deterin and survivin, has dual functions: it participates in chromosome segregation events and cytokinesis and exhibits anti-apoptotic activity. 10.1242/jcs.02902 The inhibitor-of-apoptosis protein Bir1p protects against apoptosis in S. cerevisiae and is a substrate for the yeast homologue of Omi/HtrA2 David Walter Silke Wissing Frank Madeo Birthe Fahrenkrog doi:10.1242/jcs.02902 J Cell Sci, Vol. 119, No. 9. (1 May 2006), pp. 1843-1851. 2008-05-20T20:53:55-00:00 2006 J Cell Sci 119 9 1843 1851 apoptosis http://www.citeulike.org/user/hplatero/article/2817415 <i>J. Cell Biol., Vol. 175, No. 4. (20 November 2006), pp. 521-525.</i><br /><br />The purpose of apoptosis in multicellular organisms is obvious: single cells die for the benefit of the whole organism (for example, during tissue development or embryogenesis). Although apoptosis has also been shown in various microorganisms, the reason for this cell death program has remained unexplained. Recently published studies have now described yeast apoptosis during aging, mating, or exposure to killer toxins (Fabrizio, P., L. Battistella, R. Vardavas, C. Gattazzo, L.L. Liou, A. Diaspro, J.W. Dossen, E.B. Gralla, and V.D. Longo. 2004. J. Cell Biol. 166:1055-1067; Herker, E., H. Jungwirth, K.A. Lehmann, C. Maldener, K.U. Frohlich, S. Wissing, S. Buttner, M. Fehr, S. Sigrist, and F. Madeo. 2004. J. Cell Biol. 164:501-507, underscoring the evolutionary benefit of a cell suicide program in yeast and, thus, giving a unicellular organism causes to die for. 10.1083/jcb.200608098 Why yeast cells can undergo apoptosis: death in times of peace, love, and war Sabrina Buttner Tobias Eisenberg Eva Herker Didac Carmona-Gutierrez Guido Kroemer Frank Madeo doi:10.1083/jcb.200608098 J. Cell Biol., Vol. 175, No. 4. (20 November 2006), pp. 521-525. 2008-05-20T18:26:25-00:00 2006 J. Cell Biol. 175 4 521 525 apoptosis http://www.citeulike.org/user/hplatero/article/2817400 <i>Mol. Biol. Cell, Vol. 14, No. 2. (1 February 2003), pp. 721-729.</i><br /><br />The LSM4 gene of Saccharomyces cerevisiae codes for an essential protein involved in pre-mRNA splicing and also in mRNA decapping, a crucial step for mRNA degradation. We previously demonstrated that the first 72 amino acids of the Kluyveromyces lactis Lsm4p (KlLsm4p), which contain the Sm-like domains, can restore cell viability in both K. lactis and S. cerevisiae cells not expressing the endogenous protein. However, the absence of the carboxy-terminal region resulted in a remarkable loss of viability in stationary phase cells (Mazzoni and Falcone, 2001). Herein, we demonstrate that S. cerevisiae cells expressing the truncated LSM4 protein of K. lactis showed the phenotypic markers of yeast apoptosis such as chromatin condensation, DNA fragmentation, and accumulation of reactive oxygen species. The study of deletion mutants revealed that apoptotic markers were clearly evident also in strains lacking genes involved in mRNA decapping, such as LSM1, DCP1, and DCP2, whereas a slight effect was observed in strains lacking the genes DHH1 and PAT1. This is the first time that a connection between mRNA stability and apoptosis is reported in yeast, pointing to mRNA decapping as the crucial step responsible of the observed apoptotic phenotypes. 10.1091/mbc.E02-05-0258 A Truncated Form of KlLsm4p and the Absence of Factors Involved in mRNA Decapping Trigger Apoptosis in Yeast Cristina Mazzoni Patrizia Mancini Loredana Verdone Frank Madeo Agnese Serafini Eva Herker Claudio Falcone doi:10.1091/mbc.E02-05-0258 Mol. Biol. Cell, Vol. 14, No. 2. (1 February 2003), pp. 721-729. 2008-05-20T18:11:02-00:00 2003 Mol. Biol. Cell 14 2 721 729 apoptosis http://www.citeulike.org/user/hplatero/article/2817157 <i>FEMS Yeast Research, Vol. 4, No. 1. (2003), pp. 7-13.</i><br /><br />Abstract Sugars induce death of Saccharomyces cerevisiae within a few hours in the absence of additional nutrients to support growth; by contrast, cells incubated in water or in the presence of other nutrients without sugar remain viable for weeks. Here we show that this sugar-induced cell death (SICD) is characterized by rapid production of reactive oxygen species (ROS), RNA and DNA degradation, membrane damage, nucleus fragmentation and cell shrinkage. Addition of ascorbic acid to sugar-incubated cells prevents SICD, indicating that SICD is initiated by ROS. The lack of a protection mechanism against SICD suggests that sugars use to be the limiting nutrients for yeast and are probably depleted before all other nutrients. Being the limiting nutrient, sugars became the growth-stimulating agent, signaling the presence of sufficient nutrients for growth, but in the absence of the complementing nutrients they induce apoptotic death. Sugar-induced apoptosis in yeast cells David Granot Alex Levine Edan Hefetz doi:10.1016/S1567-1356(03)00154-5 FEMS Yeast Research, Vol. 4, No. 1. (2003), pp. 7-13. 2008-05-20T16:33:46-00:00 2003 FEMS Yeast Research 4 1 7 13 apoptosis http://www.citeulike.org/user/hplatero/article/2817153 <i>Experimental Gerontology, Vol. 37, No. 1. (December 2001), pp. 27-31.</i><br /><br />Apoptosis is a form of programmed cell death with a central role in development and homeostasis of metazoan organisms. Recent research indicates the presence of an apoptotic cell death program in unicellular eukaryotes. Yeast can be killed by expression of mammalian proapoptotic genes or in response to oxygen stress, which is an inducer of mammalian apoptosis. The dying yeast cells show morphological alterations typical for apoptosis. Yeast provides a simple model for cellular aging. The observation that old yeast cells produce oxygen radicals and die apoptotically may provide clues to a similar sequence of events in mammalian aging. Apoptosis in yeast: a new model for aging research Kai-Uwe Fröhlich Frank Madeo doi:10.1016/S0531-5565(01)00177-2 Experimental Gerontology, Vol. 37, No. 1. (December 2001), pp. 27-31. 2008-05-20T16:31:51-00:00 2001 Experimental Gerontology 37 1 27 31 apoptosis http://www.citeulike.org/user/hplatero/article/2814454 <i>PLoS biology, Vol. 2, No. 10. (October 2004)</i><br /><br />Stem cells resident in adult tissues are principally quiescent, yet harbor enormous capacity for proliferation to achieve self renewal and to replenish their tissue constituents. Although a single hematopoietic stem cell (HSC) can generate sufficient primitive progeny to repopulate many recipients, little is known about the molecular mechanisms that maintain their potency or regulate their self renewal. Here we have examined the gene expression changes that occur over a time course when HSCs are induced to proliferate and return to quiescence in vivo. These data were compared to data representing differences between naturally proliferating fetal HSCs and their quiescent adult counterparts. Bioinformatic strategies were used to group time-ordered gene expression profiles generated from microarrays into signatures of quiescent and dividing stem cells. A novel method for calculating statistically significant enrichments in Gene Ontology groupings for our gene lists revealed elemental subgroups within the signatures that underlie HSC behavior, and allowed us to build a molecular model of the HSC activation cycle. Initially, quiescent HSCs evince a state of readiness. The proliferative signal induces a preparative state, which is followed by active proliferation divisible into early and late phases. Re-induction of quiescence involves changes in migratory molecule expression, prior to reestablishment of homeostasis. We also identified two genes that increase in both gene and protein expression during activation, and potentially represent new markers for proliferating stem cells. These data will be of use in attempts to recapitulate the HSC self renewal process for therapeutic expansion of stem cells, and our model may correlate with acquisition of self renewal characteristics by cancer stem cells. Molecular signatures of proliferation and quiescence in hematopoietic stem cells. TA Venezia AA Merchant CA Ramos NL Whitehouse AS Young CA Shaw MA Goodell doi:10.1371/journal.pbio.0020301 PLoS biology, Vol. 2, No. 10. (October 2004) 2008-05-19T23:06:41-00:00 2004 PLoS biology 1545-7885 2 10 quiescence http://www.citeulike.org/user/hplatero/article/2814030 <i>Trends in genetics : TIG, Vol. 6, No. 2. (February 1990), pp. 36-40.</i><br /><br />Transcription factors can be divided into classes on the basis of their mode of interaction with the target promoter sequence. Different protein domains responsible for DNA recognition have been identified. In this review we discuss the leucine zipper structure, which has been found in several nuclear factors, including the oncoproteins Fos and Jun. Structural considerations are summarized to help understand how dimerization is mediated by the leucine zipper and how this is the prerequisite for optimal target DNA recognition by the adjacent basic domains. Dimers, leucine zippers and DNA-binding domains. SJ Busch P Sassone-Corsi Trends in genetics : TIG, Vol. 6, No. 2. (February 1990), pp. 36-40. 2008-05-19T19:55:36-00:00 1990 Trends in genetics : TIG 0168-9525 6 2 36 40 bzip http://www.citeulike.org/user/hplatero/article/2814029 <i>Science, Vol. 240 (1988), pp. 1759-1764.</i> The leucine zipper: a hypothetical structure common to a new class of DNA binding proteins. Landschulz Science, Vol. 240 (1988), pp. 1759-1764. 2008-05-19T19:55:15-00:00 1988 Science 240 1759 1764 bzip http://www.citeulike.org/user/hplatero/article/2806080 <i>FEBS Letters, Vol. 425, No. 2. (27 March 1998), pp. 323-328.</i><br /><br />Four putative yeast transcription factors (Hal6-9p) have been identified which upon overexpression in multicopy plasmids increase sodium and lithium tolerance. This effect is mediated, at least in part, by increased expression of the Ena1p Na+/Li+ extrusion pump. Hal6p and Hal7p are bZIP proteins and their gene disruptions affected neither salt tolerance nor ENA1 expression. Hal8p and Hal9p are putative zinc fingers and their gene disruptions decreased both salt tolerance and ENA1 expression. Therefore, Hal8p and Hal9p, but not Hal6p and Hal7p, qualify as transcriptional activators of ENA1 under physiological conditions. Hal8p seems to mediate the calcineurin-dependent part of ENA1 expression. Yeast putative transcription factors involved in salt tolerance Iratxe Mendizabal Gabino Rios Jose Mulet Ramón Serrano Iñigo de Larrinoa doi:10.1016/S0014-5793(98)00249-X FEBS Letters, Vol. 425, No. 2. (27 March 1998), pp. 323-328. 2008-05-16T21:19:06-00:00 1998 FEBS Letters 425 2 323 328 bzip cin5 yap6 http://www.citeulike.org/user/hplatero/article/1391263 <i>J Mol Biol, Vol. 300, No. 2. (7 July 2000), pp. 377-402.</i><br /><br />We describe the de novo design and biophysical characterization of a model coiled-coil protein in which we have systematically substituted 20 different amino acid residues in the central "d" position. The model protein consists of two identical 38 residue polypeptide chains covalently linked at their N termini via a disulfide bridge. The hydrophobic core contained Val and Ile residues at positions "a" and Leu residues at positions "d". This core allowed for the formation of both two-stranded and three-stranded coiled-coils in benign buffer, depending on the substitution at position "d". The structure of each analog was analyzed by CD spectroscopy and their relative stability determined by chemical denaturation using GdnHCI (all analogs denatured from the two-stranded state). The oligomeric state(s) was determined by high-performance size-exclusion chromatography and sedimentation equilibrium analysis in benign medium. Our results showed a thermodynamic stability order (in order of decreasing stability) of: Leu, Met, Ile, Tyr, Phe, Val, Gln, Ala, Trp, Asn, His, Thr, Lys, Ser, Asp, Glu, Arg, Orn, and Gly. The Pro analog prevented coiled-coil formation. The overall stability range was 7.4 kcal/mol from the lowest to the highest analog, indicating the importance of the hydrophobic core and the dramatic effect a single substitution in the core can have upon the stability of the protein fold. In general, the side-chain contribution to the level of stability correlated with side-chain hydrophobicity. Molecular modelling studies, however, showed that packing effects could explain deviations from a direct correlation. In regards to oligomerization state, eight analogs demonstrated the ability to populate exclusively one oligomerization state in benign buffer (0.1 M KCl, 0.05 M K(2)PO(4)(pH 7)). Ile and Val (the beta-branched residues) induced the three-stranded oligomerization state, whereas Tyr, Lys, Arg, Orn, Glu and Asp induced the two-stranded state. Asn, Gln, Ser, Ala, Gly, Phe, Leu, Met and Trp analogs were indiscriminate and populated two-stranded and three-stranded states. Comparison of these results with similar substitutions in position "a" highlights the positional effects of individual residues in defining the stability and numbers of polypeptide chains occurring in a coiled-coil structure. Overall, these results in conjunction with other work now generate a relative thermodynamic stability scale for 19 naturally occurring amino acid residues in either an "a" or "d" position of a two-stranded coiled-coil. Thus, these results will aid in the de novo design of new coiled-coil structures, a better understanding of their structure/function relationships and the design of algorithms to predict the presence of coiled-coils within native protein sequences. Effects of side-chain characteristics on stability and oligomerization state of a de novo-designed model coiled-coil: 20 amino acid substitutions in position "d". B Tripet K Wagschal P Lavigne CT Mant RS Hodges doi:10.1006/jmbi.2000.3866 J Mol Biol, Vol. 300, No. 2. (7 July 2000), pp. 377-402. 2007-06-15T04:07:15-00:00 2000 J Mol Biol 0022-2836 300 2 377 402 bzip http://www.citeulike.org/user/hplatero/article/2802789 <i>Biochemistry, Vol. 36 (1997), pp. 12567-12573.</i> Leucine Is the Most Stabilizing Aliphatic Amino Acid in the d Position of a Dimeric Leucine Zipper Coiled Coil Jaideep Biochemistry, Vol. 36 (1997), pp. 12567-12573. 2008-05-15T23:01:15-00:00 1997 Biochemistry 36 12567 12573 bzip http://www.citeulike.org/user/hplatero/article/2800792 <i>J. Biol. Chem., Vol. 274, No. 13. (26 March 1999), pp. 8949-8957.</i><br /><br />Upon transforming growth factor-[beta] (TGF-[beta]) binding to its cognate receptor, Smad3 and Smad4 form heterodimers and transduce the TGF-[beta] signal to the nucleus. In addition to the Smad pathway, another pathway involving a member of the mitogen-activated protein kinase kinase kinase family of kinases, TGF-[beta]-activated kinase-1 (TAK1), is required for TGF-[beta] signaling. However, it is unknown how these pathways function together to synergistically amplify TGF-[beta] signaling. Here we report that the transcription factor ATF-2 (also called CRE-BP1) is bound by a hetero-oligomer of Smad3 and Smad4 upon TGF-[beta] stimulation. ATF-2 is one member of the ATF/CREB family that binds to the cAMP response element, and its activity is enhanced after phosphorylation by stress-activated protein kinases such as c-Jun N-terminal kinase and p38. The binding between ATF-2 and Smad3/4 is mediated via the MH1 region of the Smad proteins and the basic leucine zipper region of ATF-2. TGF-[beta] signaling also induces the phosphorylation of ATF-2 via TAK1 and p38. Both of these actions are shown to be responsible for the synergistic stimulation of ATF-2 trans-activating capacity. These results indicate that ATF-2 plays a central role in TGF-[beta] signaling by acting as a common nuclear target of both Smad and TAK1 pathways. 10.1074/jbc.274.13.8949 ATF-2 Is a Common Nuclear Target of Smad and TAK1 Pathways in Transforming Growth Factor-beta Signaling Yuji Sano Jun Harada Shigeki Tashiro Ryoko Gotoh-Mandeville Toshio Maekawa Shunsuke Ishii doi:10.1074/jbc.274.13.8949 J. Biol. Chem., Vol. 274, No. 13. (26 March 1999), pp. 8949-8957. 2008-05-15T06:09:14-00:00 1999 J. Biol. Chem. 274 13 8949 8957 atf creb http://www.citeulike.org/user/hplatero/article/2800789 <i>J. Neurosci., Vol. 19, No. 22. (15 November 1999), pp. 9821-9830.</i><br /><br />Iron chelators are pluripotent neuronal antiapoptotic agents that have been shown to enhance metabolic recovery in cerebral ischemia models. The precise mechanism(s) by which these agents exert their effects remains unclear. Recent studies have demonstrated that iron chelators activate a hypoxia signal transduction pathway in non-neuronal cells that culminates in the stabilization of the transcriptional activator hypoxia-inducible factor-1 (HIF-1) and increased expression of gene products that mediate hypoxic adaptation. We examined the hypothesis that iron chelators prevent oxidative stress-induced death in cortical neuronal cultures by inducing expression of HIF-1 and its target genes. We report that the structurally distinct iron chelators deferoxamine mesylate and mimosine prevent apoptosis induced by glutathione depletion and oxidative stress in embryonic cortical neuronal cultures. The protective effects of iron chelators are correlated with their ability to enhance DNA binding of HIF-1 and activating transcription factor 1(ATF-1)/cAMP response element-binding protein (CREB) to the hypoxia response element in cortical cultures and the H19-7 hippocampal neuronal cell line. We show that mRNA, protein, and/or activity levels for genes whose expression is known to be regulated by HIF-1, including glycolytic enzymes, p21waf1/cip1, and erythropoietin, are increased in cortical neuronal cultures in response to iron chelator treatment. Finally, we demonstrate that cobalt chloride, which also activates HIF-1 and ATF-1/CREB in cortical cultures, also prevents oxidative stress-induced death in these cells. Altogether, these results suggest that iron chelators exert their neuroprotective effects, in part, by activating a signal transduction pathway leading to increased expression of genes known to compensate for hypoxic or oxidative stress. Protection from Oxidative Stress-Induced Apoptosis in Cortical Neuronal Cultures by Iron Chelators Is Associated with Enhanced DNA Binding of Hypoxia-Inducible Factor-1 and ATF-1/CREB and Increased Expression of Glycolytic Enzymes, p21waf1/cip1, and Erythropoietin Khalequz Zaman Hoon Ryu David Hall Kevin O'Donovan Kuo-I Lin Matthew Miller John Marquis Jay Baraban Gregg Semenza Rajiv Ratan J. Neurosci., Vol. 19, No. 22. (15 November 1999), pp. 9821-9830. 2008-05-15T06:04:10-00:00 1999 J. Neurosci. 19 22 9821 9830 atf creb http://www.citeulike.org/user/hplatero/article/2800365 <i>Mol. Cell. Biol., Vol. 21, No. 14. (15 July 2001), pp. 4441-4452.</i><br /><br />We previously described the identification of quail MafA, a novel transcription factor of the Maf bZIP (basic region leucine zipper) family, expressed in the differentiating neuroretina (NR). In the present study, we provide the first evidence that MafA is phosphorylated and that its biological properties strongly rely upon phosphorylation of serines 14 and 65, two residues located in the transcriptional activating domain within a consensus for phosphorylation by mitogen-activated protein kinases and which are conserved among Maf proteins. These residues are phosphorylated by ERK2 but not by p38, JNK, and ERK5 in vitro. However, the contribution of the MEK/ERK pathway to MafA phosphorylation in vivo appears to be moderate, implicating another kinase. The integrity of serine 14 and serine 65 residues is required for transcriptional activity, since their mutation into alanine severely impairs MafA capacity to activate transcription. Furthermore, we show that the MafA S14A/S65A mutant displays reduced capacity to induce expression of QR1, an NR-specific target of Maf proteins. Likewise, the integrity of serines 14 and 65 is essential for the MafA ability to stimulate expression of crystallin genes in NR cells and to induce NR-to-lens transdifferentiation. Thus, the MafA capacity to induce differentiation programs is dependent on its phosphorylation. 10.1128/MCB.21.14.4441-4452.2001 Phosphorylation of MafA Is Essential for Its Transcriptional and Biological Properties Sofia Benkhelifa Sylvain Provot Eugene Nabais Alain Eychene Georges Calothy Marie-Paule Felder-Schmittbuhl doi:10.1128/MCB.21.14.4441-4452.2001 Mol. Cell. Biol., Vol. 21, No. 14. (15 July 2001), pp. 4441-4452. 2008-05-15T00:20:47-00:00 2001 Mol. Cell. Biol. 21 14 4441 4452 maf http://www.citeulike.org/user/hplatero/article/2800355 <i>J. Biol. Chem., Vol. 275, No. 29. (14 July 2000), pp. 22166-22171.</i><br /><br />In Caenorhabditis elegans, the predicted transcription factor SKN-1 is required for embryonic endodermal and mesodermal specification and for maintaining differentiated intestinal cells post-embryonically. The SKN-1 DNA-binding region is related to the Cap`n'Collar (CNC) family of basic leucine zipper proteins, but uniquely, SKN-1 binds DNA as a monomer. CNC proteins are absent in C. elegans, however; and their involvement in the endoderm and mesoderm suggests some functional parallels to SKN-1. Using a cell culture assay, we show that SKN-1 induces transcription and contains three potent activation domains. The functional core of one domain is a short motif, the DIDLID element, which is highly conserved in a subgroup of vertebrate CNC proteins. The DIDLID element is important for SKN-1-driven transcription, suggesting a likely significance in other CNC proteins. SKN-1 binds to and activates transcription through the p300/cAMP-responsive element-binding protein-binding protein (CBP) coactivator, supporting the genetic prediction that SKN-1 recruits the C. elegans p300/CBP ortholog, CBP-1. The DIDLID element appears to act independently of p300/CBP, however, suggesting a distinct conserved target. The evolutionarily preservation of the DIDLID transcriptional element supports the model that SKN-1 and some CNC proteins interact with analogous cofactors and may have preserved some similar functions despite having divergent DNA-binding domains. 10.1074/jbc.M001746200 A Conserved Transcription Motif Suggesting Functional Parallels between Caenorhabditis elegans SKN-1 and Cap`n'Collar-related Basic Leucine Zipper Proteins Amy Walker Raymond See Ceri Batchelder Thip Kophengnavong Timothy Gronniger Yang Shi Keith Blackwell doi:10.1074/jbc.M001746200 J. Biol. Chem., Vol. 275, No. 29. (14 July 2000), pp. 22166-22171. 2008-05-15T00:16:45-00:00 2000 J. Biol. Chem. 275 29 22166 22171 skn-1 http://www.citeulike.org/user/hplatero/article/2796913 <i>Proceedings of the National Academy of Sciences, Vol. 84, No. 10. (15 May 1987), pp. 3316-3319.</i><br /><br />The product of the recently described oncogene jun shows significant amino acid sequence homology with the GCN4 yeast transcriptional activator protein. The similarity is restricted to the 66 carboxyl-terminal amino acids, thought to be the DNA-binding domain of the GCN4 protein. In these [alpha] -helix-permissive regions of the jun and GCN4 products there is also a lesser but still significant amino acid resemblance to the fos protein and a marginal degree of similarity to myc proteins. The amino acid sequence homology between GCN4 and jun gene products suggests that the jun protein may bind to DNA in a sequence-specific way and exert a regulatory function. 10.1073/pnas.84.10.3316 Homology between the DNA-Binding Domain of the GCN4 Regulatory Protein of Yeast and the Carboxyl-Terminal Region of a Protein Coded for by the Oncogene jun Peter Vogt Timothy Bos Russell Doolittle doi:10.1073/pnas.84.10.3316 Proceedings of the National Academy of Sciences, Vol. 84, No. 10. (15 May 1987), pp. 3316-3319. 2008-05-14T07:16:15-00:00 1987 Proceedings of the National Academy of Sciences 84 10 3316 3319 first_paper http://www.citeulike.org/user/hplatero/article/2102609 <i>Proceedings of the National Academy of Sciences (12 December 2007), 0706339104.</i><br /><br />As whole-genome proteinprotein interaction datasets become available for a wide range of species, evolutionary biologists have the opportunity to address some of the unanswered questions surrounding the evolution of these complex systems. Protein interaction networks from divergent organisms may be compared to investigate how gene duplication, deletion, and rewiring processes have shaped the evolution of their contemporary structures. However, current approaches for comparing observed networks from multiple species lack the phylogenetic context necessary to reconstruct the evolutionary history of a network. Here we show how probabilistic modeling can provide a platform for the quantitative analysis of multiple protein interaction networks. We apply this technique to the reconstruction of ancestral networks for the bZIP family of transcription factors and find that excellent agreement is obtained with an alternative sequence-based method for the prediction of leucine zipper interactions. Further analysis shows our probabilistic method to be significantly more robust to the presence of noise in the observed network data than a simple parsimony-based approach. In addition, the integration of evidence over multiple species means that the same method may be used to improve the quality of noisy interaction data for extant species. The ancestral states of a protein interaction network have been reconstructed here by using an explicit probabilistic model of network evolution. We anticipate that this model will form the basis of more general methods for probing the evolutionary history of biochemical networks. 10.1073/pnas.0706339104 Reconstruction of ancestral protein interaction networks for the bZIP transcription factors John Pinney Grigoris Amoutzias Magnus Rattray David Robertson doi:10.1073/pnas.0706339104 Proceedings of the National Academy of Sciences (12 December 2007), 0706339104. 2007-12-13T08:12:10-00:00 2007 Proceedings of the National Academy of Sciences 0706339104 bzip http://www.citeulike.org/user/hplatero/article/2796697 <i>J Cell Sci, Vol. 117, No. 25. (1 December 2004), pp. 5965-5973.</i><br /><br />The AP-1 transcription factor is mainly composed of Jun, Fos and ATF protein dimers. It mediates gene regulation in response to a plethora of physiological and pathological stimuli, including cytokines, growth factors, stress signals, bacterial and viral infections, as well as oncogenic stimuli. Studies in genetically modified mice and cells have highlighted a crucial role for AP-1 in a variety of cellular events involved in normal development or neoplastic transformation causing cancer. However, emerging evidence indicates that the contribution of AP-1 to determination of cell fates critically depends on the relative abundance of AP-1 subunits, the composition of AP-1 dimers, the quality of stimulus, the cell type and the cellular environment. Therefore, AP-1-mediated regulation of processes such as proliferation, differentiation, apoptosis and transformation should be considered within the context of a complex dynamic network of signalling pathways and other nuclear factors that respond simultaneously. 10.1242/jcs.01589 AP-1 subunits: quarrel and harmony among siblings Jochen Hess Peter Angel Marina Schorpp-Kistner doi:10.1242/jcs.01589 J Cell Sci, Vol. 117, No. 25. (1 December 2004), pp. 5965-5973. 2008-05-14T06:05:40-00:00 2004 J Cell Sci 117 25 5965 5973 bzip http://www.citeulike.org/user/hplatero/article/2796657 <i>The EMBO journal, Vol. 15, No. 10. (15 May 1996), pp. 2519-2529.</i><br /><br />Transcription activation of sulfur metabolism in yeast is dependent on two DNA binding factors, the centromere binding factor 1 (Cbf1) and Met4. While the role of Met4 was clearly established by showing that it acts as a transcription activator, the precise function in transcription of the multi-functional factor Cbf1 remains more elusive. We report here the identification of a new transcription factor Met28 which participates in the regulation of sulfur metabolism. Cloning and sequencing of MET28 revealed that it encodes a new member of the basic leucine zipper DNA binding factor family. We also demonstrate that Met28 possesses no intrinsic transcription activation capabilities. Studies of the DNA binding characteristics of Met28 led us to identify in gel mobility assays a heteromeric complex containing Cbf1, Met4 and Met28. We further demonstrated that the presence of Cbf1 and Met4 stimulates the binding of Met28 to DNA. 'Two-hybrid' studies allowed us to carry out preliminary investigations on the binary protein-protein interactions involved in the formation of the Cbf1-Met4-Met28 complex. Our results give evidence that the leucine zippers of Met4 and Met28, along with the basic helix-loop-helix domain of Cbf1, provide the protein surfaces mediating these interactions. All these results suggest that the multi-functional factor Cbf1 functions in transcription activation by tethering specific activating factors to the DNA. A heteromeric complex containing the centromere binding factor 1 and two basic leucine zipper factors, Met4 and Met28, mediates the transcription activation of yeast sulfur metabolism. L Kuras H Cherest Y Surdin-Kerjan D Thomas The EMBO journal, Vol. 15, No. 10. (15 May 1996), pp. 2519-2529. 2008-05-14T05:19:50-00:00 1996 The EMBO journal 0261-4189 15 10 2519 2529 first_paper http://www.citeulike.org/user/hplatero/article/2796579 <i>Mol. Cell. Biol., Vol. 20, No. 12. (15 June 2000), pp. 4340-4349.</i><br /><br />In Saccharomyces cerevisiae, the family of ATF/CREB transcriptional regulators consists of a repressor, Acr1 (Sko1), and two activators, Aca1 and Aca2. The AP-1 factor Gen4 does not activate transcription through ATF/CREB sites in vivo even though it binds these sites in vitro. Unlike ATF/CREB activators in other species, Aca1- and Aca2-dependent transcription is not affected by protein kinase A or by stress, and Aca1 and Aca2 are not required for Hog1-dependent salt induction of transcription through an optimal ATF/CREB site. Aca2 is important for a variety of biological functions including growth on nonoptimal carbon sources, and Aca2-dependent activation is modestly regulated by carbon source. Strains lacking Aca1 are phenotypically normal, but overexpression of Aca1 suppresses some defects associated with the loss of Aca2, indicating a functional overlap between Aca1 and Aca2. Acr1 represses transcription both by recruiting the Cyc8-Tup1 corepressor and by directly competing with Aca1 and Aca2 for target sites. Acr1 does not fully account for osmotic regulation through ATF/CREB sites, and a novel Hog1-dependent activator(s) that is not a bZIP protein is required for ATF/CREB site activation in response to high salt. In addition, Acr1 does not affect a number of phenotypes that arise from loss of Aca2. Thus, members of the S. cerevisiae ATF/CREB family have overlapping, but distinct, biological functions and target genes. 10.1128/MCB.20.12.4340-4349.2000 Aca1 and Aca2, ATF/CREB Activators in Saccharomyces cerevisiae, Are Important for Carbon Source Utilization but Not the Response to Stress Adelaida Garcia-Gimeno Kevin Struhl doi:10.1128/MCB.20.12.4340-4349.2000 Mol. Cell. Biol., Vol. 20, No. 12. (15 June 2000), pp. 4340-4349. 2008-05-14T04:09:15-00:00 2000 Mol. Cell. Biol. 20 12 4340 4349 first_paper http://www.citeulike.org/user/hplatero/article/2796571 <i>Proceedings of the National Academy of Sciences of the United States of America, Vol. 86, No. 1. (January 1989), pp. 109-113.</i><br /><br />Activating transcription factor (ATF) is a mammalian transcriptional activator, which is involved in the expression of many viral E1a-inducible and cellular cAMP-inducible genes. Here we identify from the yeast Saccharomyces cerevisiae a previously uncharacterized protein whose DNA binding specificity is like mammalian ATF. We purify this protein (yATF) and show that it is a 66-kDa polypeptide. Finally, we demonstrate that a mammalian ATF site can function as an upstream activating sequence in S. cerevisiae. Taken together, our results suggest that yATF is a previously uncharacterized S. cerevisiae transcriptional activator. Identification and purification of a Saccharomyces cerevisiae protein with the DNA binding specificity of mammalian activating transcription factor. YS Lin MR Green Proceedings of the National Academy of Sciences of the United States of America, Vol. 86, No. 1. (January 1989), pp. 109-113. 2008-05-14T03:56:09-00:00 1989 Proceedings of the National Academy of Sciences of the United States of America 0027-8424 86 1 109 113 bzip http://www.citeulike.org/user/hplatero/article/122002 <i>Microbiol Mol Biol Rev, Vol. 69, No. 1. (March 2005), pp. 79-100.</i><br /><br />Target of rapamycin (TOR) proteins are members of the phosphatidylinositol kinase-related kinase (PIKK) family and are highly conserved from yeast to mammals. TOR proteins integrate signals from growth factors, nutrients, stress, and cellular energy levels to control cell growth. The ribosomal S6 kinase 1 (S6K) and eukaryotic initiation factor 4E binding protein 1(4EBP1) are two cellular targets of TOR kinase activity and are known to mediate TOR function in translational control in mammalian cells. However, the precise molecular mechanism of TOR regulation is not completely understood. One of the recent breakthrough studies in TOR signaling resulted in the identification of the tuberous sclerosis complex gene products, TSC1 and TSC2, as negative regulators for TOR signaling. Furthermore, the discovery that the small GTPase Rheb is a direct downstream target of TSC1-TSC2 and a positive regulator of the TOR function has significantly advanced our understanding of the molecular mechanism of TOR activation. Here we review the current understanding of the regulation of TOR signaling and discuss its function as a signaling nexus to control cell growth during normal development and tumorigenesis. Signaling by target of rapamycin proteins in cell growth control. K Inoki H Ouyang Y Li KL Guan doi:10.1128/MMBR.69.1.79-100.2005 Microbiol Mol Biol Rev, Vol. 69, No. 1. (March 2005), pp. 79-100. 2005-03-11T16:53:38-00:00 2005 Microbiol Mol Biol Rev 1092-2172 69 1 79 100 rapamycin tor http://www.citeulike.org/user/hplatero/article/2776358 <i>Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Vol. In Press, Corrected Proof</i><br /><br />Apoptosis is associated in many cases with the generation of reactive oxygen species (ROS) in cells across a wide range of organisms including lower eukaryotes such as the yeast Saccharomyces cerevisiae. Currently there are many unresolved questions concerning the relationship between apoptosis and the generation of ROS. These include which ROS are involved in apoptosis, what mechanisms and targets are important and whether apoptosis is triggered by ROS damage or ROS are generated as a consequence or part of the cellular disruption that occurs during cell death. Here we review the nature of the ROS involved, the damage they cause to cells, summarise the responses of S. cerevisiae to ROS and discuss those aspects in which ROS affect cell integrity that may be relevant to the apoptotic process. Reactive oxygen species and yeast apoptosis Gabriel Perrone Shi-Xiong Tan Ian Dawes doi:10.1016/j.bbamcr.2008.01.023 Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Vol. In Press, Corrected Proof 2008-05-09T17:31:49-00:00 Biochimica et Biophysica Acta (BBA) - Molecular Cell Research In Press, Corrected Proof apoptosis http://www.citeulike.org/user/hplatero/article/2767676 <i>J Cell Sci, Vol. 117, No. 1. (1 January 2004), pp. 115-126.</i><br /><br />The yeast S. cerevisiae can undergo programmed cell death that exhibits the typical cellular markers of apoptosis. The mammalian HtrA2 protein was recently reported to mediate apoptosis in a serine-protease-dependent manner owing to its ability to antagonise the inhibitor of apoptosis protein XIAP. Here, we report the identification and characterisation of the S. cerevisiae HtrA-like protein, which we termed Nma111p (for nuclear mediator of apoptosis), as a mediator of yeast apoptosis. Nma111p is a nuclear protein that, under cellular stress conditions (i.e. at elevated temperature or after induction of apoptosis by H2O2), tends to aggregate inside the nucleus without its expression level being upregulated, suggesting that aggregation of Nma111p is correlated to its death-mediating character. Nma111p belongs to the HtrA family of serine proteases and its pro-apoptotic activity depends on its serine-protease activity. Yeast cells that lack Nma111p survive better at 50degreesC than wild-type cells and the cells show no apoptotic hallmarks, such as chromatin condensation and fragmentation, or accumulation of reactive oxygen species, after the induction of apoptosis by H2O2. By contrast, overexpression of Nma111p enhances apoptotic-like cell death. Therefore, Nma111p, like its mammalian homologue HtrA2, mediates apoptosis. 10.1242/jcs.00848 The S. cerevisiae HtrA-like protein Nma111p is a nuclear serine protease that mediates yeast apoptosis Birthe Fahrenkrog Ursula Sauder Ueli Aebi doi:10.1242/jcs.00848 J Cell Sci, Vol. 117, No. 1. (1 January 2004), pp. 115-126. 2008-05-07T23:21:21-00:00 2004 J Cell Sci 117 1 115 126 apoptosis http://www.citeulike.org/user/hplatero/article/355421 <i>Curr Opin Microbiol, Vol. 7, No. 6. (December 2004), pp. 655-660.</i><br /><br />Apoptosis is a highly regulated cellular suicide program crucial for metazoan development. However, dysfunction of apoptosis also leads to several diseases. Yeast undergoes apoptosis after application of acetic acid, sugar- or salt-stress, plant antifungal peptides, or hydrogen peroxide. Oxygen radicals seem to be key elements of apoptotic execution, conserved during evolution. Furthermore, several yeast orthologues of central metazoan apoptotic regulators have been identified, such as a caspase and a caspase-regulating serine protease. In addition, physiological occurrence of cell death has been detected during aging and mating in yeast. The finding of apoptosis in yeast, other fungi and parasites is not only of great medical relevance but will also help to understand some of the still unknown molecular mechanisms at the core of apoptotic execution. Apoptosis in yeast. F Madeo E Herker S Wissing H Jungwirth T Eisenberg KU Fröhlich doi:10.1016/j.mib.2004.10.012 Curr Opin Microbiol, Vol. 7, No. 6. (December 2004), pp. 655-660. 2005-10-19T22:29:30-00:00 2004 Curr Opin Microbiol 1369-5274 7 6 655 660 apoptosis http://www.citeulike.org/user/hplatero/article/2767155 <i>Nucleic Acids Research, Vol. 34 (2006), pp. D446-D451.</i> The YEASTRACT database: a tool for the analysis of transcription regulatory associations in Saccharomyces cerevisiae Miguel Nucleic Acids Research, Vol. 34 (2006), pp. D446-D451. 2008-05-07T18:49:04-00:00 2006 Nucleic Acids Research 34 D446 D451 tf_database http://www.citeulike.org/user/hplatero/article/355425 <i>Curr Genet, Vol. 41, No. 4. (July 2002), pp. 208-216.</i><br /><br />Apoptosis is a highly coordinated cellular suicide program crucial for metazoan health and diseases. Although its increasing importance in cancer, neurodegenerative disorders and AIDS led to intense research and a better understanding of apoptosis, many details of its regulation or the apoptotic phenotypes are poorly understood. The complex regulatory network and the often contradictory results obtained with human cell lines made application of an easier model system desirable. Apoptosis in yeast promises to provide a better understanding of the genetics of apoptosis. During the past 2 years, scientists were successful in identifying new cell-death regulators of humans, plants and fungi using Saccharomyces cerevisiae. The finding of apoptotic phenotypes, even in protists, suggests that apoptosis developed in unicellular organisms long before the evolutionary separation between fungi, plants and metazoan animals occurred. Apoptosis in yeast: a new model system with applications in cell biology and medicine. F Madeo S Engelhardt E Herker N Lehmann C Maldener A Proksch S Wissing KU Fröhlich doi:10.1007/s00294-002-0310-2 Curr Genet, Vol. 41, No. 4. (July 2002), pp. 208-216. 2005-10-19T22:34:53-00:00 2002 Curr Genet 0172-8083 41 4 208 216 apoptosis http://www.citeulike.org/user/hplatero/article/2762333 <i>Mol. Cell. Biol., Vol. 20, No. 9. (1 May 2000), pp. 3125-3136.</i><br /><br />The BCL-2 family includes both proapoptotic (e.g., BAX and BAK) and antiapoptotic (e.g., BCL-2 and BCL-XL) molecules. The cell death-regulating activity of BCL-2 members appears to depend on their ability to modulate mitochondrial function, which may include regulation of the mitochondrial permeability transition pore (PTP). We examined the function of BAX and BCL-XL using genetic and biochemical approaches in budding yeast because studies with yeast suggest that BCL-2 family members act upon highly conserved mitochondrial components. In this study we found that in wild-type yeast, BAX induced hyperpolarization of mitochondria, production of reactive oxygen species, growth arrest, and cell death; however, cytochrome c was not released detectably despite the induction of mitochondrial dysfunction. Coexpression of BCL-XL prevented all BAX-mediated responses. We also assessed the function of BCL-XL and BAX in the same strain of Saccharomyces cerevisiae with deletions of selected mitochondrial proteins that have been implicated in the function of BCL-2 family members. BAX-induced growth arrest was independent of the tested mitochondrial components, including voltage-dependent anion channel (VDAC), the catalytic [beta] subunit or the [delta] subunit of the F0F1-ATP synthase, mitochondrial cyclophilin, cytochrome c, and proteins encoded by the mitochondrial genome as revealed by [rho0] cells. In contrast, actual cell killing was dependent upon select mitochondrial components including the [beta] subunit of ATP synthase and mitochondrial genome-encoded proteins but not VDAC. The BCL-XL protection from either BAX-induced growth arrest or cell killing proved to be independent of mitochondrial components. Thus, BAX induces two cellular processes in yeast which can each be abrogated by BCL-XL: cell arrest, which does not require aspects of mitochondrial biochemistry, and cell killing, which does. 10.1128/MCB.20.9.3125-3136.2000 Biochemical and Genetic Analysis of the Mitochondrial Response of Yeast to BAX and BCL-XL Atan Gross Kirsten Pilcher Elizabeth Blachly-Dyson Emy Basso Jennifer Jockel Michael Bassik Stanley Korsmeyer Michael Forte doi:10.1128/MCB.20.9.3125-3136.2000 Mol. Cell. Biol., Vol. 20, No. 9. (1 May 2000), pp. 3125-3136. 2008-05-06T19:18:18-00:00 2000 Mol. Cell. Biol. 20 9 3125 3136 apoptosis http://www.citeulike.org/user/hplatero/article/2152555 <i>J Cell Biol, Vol. 164, No. 4. (16 February 2004), pp. 501-507.</i><br /><br />During the past years, yeast has been successfully established as a model to study mechanisms of apoptotic regulation. However, the beneficial effects of such a cell suicide program for a unicellular organism remained obscure. Here, we demonstrate that chronologically aged yeast cultures die exhibiting typical markers of apoptosis, accumulate oxygen radicals, and show caspase activation. Age-induced cell death is strongly delayed by overexpressing YAP1, a key transcriptional regulator in oxygen stress response. Disruption of apoptosis through deletion of yeast caspase YCA1 initially results in better survival of aged cultures. However, surviving cells lose the ability of regrowth, indicating that predamaged cells accumulate in the absence of apoptotic cell removal. Moreover, wild-type cells outlast yca1 disruptants in direct competition assays during long-term aging. We suggest that apoptosis in yeast confers a selective advantage for this unicellular organism, and demonstrate that old yeast cells release substances into the medium that stimulate survival of the clone. Chronological aging leads to apoptosis in yeast. E Herker H Jungwirth KA Lehmann C Maldener KU Fröhlich S Wissing S Büttner M Fehr S Sigrist F Madeo doi:10.1083/jcb.200310014 J Cell Biol, Vol. 164, No. 4. (16 February 2004), pp. 501-507. 2007-12-20T17:46:29-00:00 2004 J Cell Biol 0021-9525 164 4 501 507 apoptosis http://www.citeulike.org/user/hplatero/article/2751774 <i>Mol. Cell. Biol., Vol. 26, No. 13. (1 July 2006), pp. 5120-5130.</i><br /><br />The relationship between translation and mRNA turnover is critical to the regulation of gene expression. One major pathway for mRNA turnover occurs by deadenylation, which leads to decapping and subsequent 5'-to-3' degradation of the body of the mRNA. Prior to mRNA decapping, a transcript exits translation and enters P bodies to become a potential decapping substrate. To understand the transition from translation to decapping, it is important to identify the factors involved in this process. In this work, we identify Sbp1p (formerly known as Ssb1p), an abundant RNA binding protein, as a high-copy-number suppressor of a conditional allele in the decapping enzyme. Sbp1p overexpression restores normal decay rates in decapping-defective strains and increases P-body size and number. In addition, Sbp1p promotes translational repression of mRNA during glucose deprivation. Moreover, P-body formation is reduced in strains lacking Sbp1p. Sbp1p acts in conjunction with Dhh1p, as it is required for translational repression and P-body formation in pat1Delta strains under these conditions. These results identify Sbp1p as a new protein that functions in the transition of mRNAs from translation to an mRNP complex destined for decapping. 10.1128/MCB.01913-05 Sbp1p Affects Translational Repression and Decapping in Saccharomyces cerevisiae Scott Segal Travis Dunckley Roy Parker doi:10.1128/MCB.01913-05 Mol. Cell. Biol., Vol. 26, No. 13. (1 July 2006), pp. 5120-5130. 2008-05-04T00:31:03-00:00 2006 Mol. Cell. Biol. 26 13 5120 5130 no-tag