Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Export

@article{citeulike:3168025, abstract = {Multiple death signals influence mitochondria during apoptosis, yet the critical initiating event for mitochondrial dysfunction in vivo has been unclear. tBID, the caspase-activated form of a "BH3-domain-only" BCL-2 family member, triggers the homooligomerization of "multidomain" conserved proapoptotic family members BAK or BAX, resulting in the release of cytochrome c from mitochondria. We find that cells lacking both Bax and Bak, but not cells lacking only one of these components, are completely resistant to tBID-induced cytochrome c release and apoptosis. Moreover, doubly deficient cells are resistant to multiple apoptotic stimuli that act through disruption of mitochondrial function: staurosporine, ultraviolet radiation, growth factor deprivation, etoposide, and the endoplasmic reticulum stress stimuli thapsigargin and tunicamycin. Thus, activation of a "multidomain" proapoptotic member, BAX or BAK, appears to be an essential gateway to mitochondrial dysfunction required for cell death in response to diverse stimuli.}, address = {Howard Hughes Medical Institute, Departments of Pathology and Medicine, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA 02115, USA.}, author = {Wei, M. C. and Zong, W. X. and Cheng, E. H. and Lindsten, T. and Panoutsakopoulou, V. and Ross, A. J. and Roth, K. A. and MacGregor, G. R. and Thompson, C. B. and Korsmeyer, S. J.}, citeulike-article-id = {3168025}, citeulike-linkout-0 = {http://dx.doi.org/10.1126/science.1059108}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/11326099}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=11326099}, day = {27}, doi = {10.1126/science.1059108}, issn = {0036-8075}, journal = {Science (New York, N.Y.)}, keywords = {apoptosis, bcl-2, intrinsic, mitochondria}, month = {April}, number = {5517}, pages = {727--730}, posted-at = {2008-08-27 21:02:42}, priority = {0}, title = {Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death.}, url = {http://dx.doi.org/10.1126/science.1059108}, volume = {292}, year = {2001} }

TY - JOUR ID - citeulike:3168025 L3 - citeulike-article-id:3168025 N2 - Multiple death signals influence mitochondria during apoptosis, yet the critical initiating event for mitochondrial dysfunction in vivo has been unclear. tBID, the caspase-activated form of a "BH3-domain-only" BCL-2 family member, triggers the homooligomerization of "multidomain" conserved proapoptotic family members BAK or BAX, resulting in the release of cytochrome c from mitochondria. We find that cells lacking both Bax and Bak, but not cells lacking only one of these components, are completely resistant to tBID-induced cytochrome c release and apoptosis. Moreover, doubly deficient cells are resistant to multiple apoptotic stimuli that act through disruption of mitochondrial function: staurosporine, ultraviolet radiation, growth factor deprivation, etoposide, and the endoplasmic reticulum stress stimuli thapsigargin and tunicamycin. Thus, activation of a "multidomain" proapoptotic member, BAX or BAK, appears to be an essential gateway to mitochondrial dysfunction required for cell death in response to diverse stimuli. IS - 5517 JF - Science (New York, N.Y.) SN - 0036-8075 AD - Howard Hughes Medical Institute, Departments of Pathology and Medicine, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA 02115, USA. EP - 730 TI - Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. VL - 292 SP - 727 KW - apoptosis KW - bcl-2 KW - intrinsic KW - mitochondria AU - Wei, MC AU - Zong, WX AU - Cheng, EH AU - Lindsten, T AU - Panoutsakopoulou, V AU - Ross, AJ AU - Roth, KA AU - MacGregor, GR AU - Thompson, CB AU - Korsmeyer, SJ PY - 2001/04/27/ UR - http://dx.doi.org/10.1126/science.1059108 ER -