CDK13: A NEW POTENTIAL HIV-1 INHIBITORY FACTOR REGULATING VIRAL mRNA SPLICING Export

@article{citeulike:2819515, abstract = {The human immunodeficiency virus type 1 (HIV-1) Tat is a 14 kDa viral protein that acts as a potent transactivator by binding to TAR (transactivation-responsive region), a structured RNA element located at the 5' end of all HIV-1 transcripts. Tat transactivates viral gene expression by inducing the phosphorylation of the C-terminal domain (CTD) of RNA Pol II through several Tat-activated kinases and by recruiting chromatin remodeling complexes and histone modifying enzymes to the HIV-1 LTR. Histone acetyl-transferases (HATs), including p300 and hGCN5, not only acetylate histones but also acetylate Tat at lysine positions 50 and 51 in the arginine-rich motif (ARM). Acetylated Tat (AcTat) at positions 50 and 51 interacts with a specialized protein module, the bromodomain, and recruits novel factors having this particular domain such as P/CAF and SWI/SNF. Other than its effect on transcription, Tat has been shown to be involved in splicing. In this study, we demonstrate that Tat interacts with CDK13 both in vivo and in vitro. We also found that CDK13 increases HIV-1 mRNA splicing and favours the production of the doubly-spliced protein Nef. In addition, we demonstrate that CDK13 acts as a possible restriction factor, in that its overexpression decreases the production of the viral proteins Gag and Env and subsequently suppresses virus production. Using siRNA against CDK13, we show that silencing of CDK13 leads to a significant increase in virus production. Finally, we demonstrate that CDK13 mediates its effect on splicing through the phosphorylation of ASF/SF2. 10.1128/JVI.02543-07}, author = {Berro, Reem and Pedati, Caitlin and Kehn-Hall, Kylene and Wu, Weilin and Klase, Zachary and Even, Yasmine and Geneviere, Anne-Marie and Ammosova, Tatiana and Nekhai, Sergei and Kashanchi, Fatah}, citeulike-article-id = {2819515}, citeulike-linkout-0 = {http://dx.doi.org/10.1128/JVI.02543-07}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18480452}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18480452}, day = {14}, doi = {10.1128/JVI.02543-07}, journal = {J. Virol.}, keywords = {aids, asfsf2, cdc2-related, cdc2l5, cdk13, ched, cycl, cyclin, cyclin-l, factor, hiv, kinase, mrna, restriction, sea, splicing, tat, transactivation, urchin, virus}, month = {May}, pages = {JVI.02543-07+}, posted-at = {2008-07-08 15:30:39}, priority = {2}, title = {CDK13: A NEW POTENTIAL HIV-1 INHIBITORY FACTOR REGULATING VIRAL mRNA SPLICING}, url = {http://dx.doi.org/10.1128/JVI.02543-07}, year = {2008} }

TY - JOUR ID - citeulike:2819515 L3 - citeulike-article-id:2819515 N2 - The human immunodeficiency virus type 1 (HIV-1) Tat is a 14 kDa viral protein that acts as a potent transactivator by binding to TAR (transactivation-responsive region), a structured RNA element located at the 5' end of all HIV-1 transcripts. Tat transactivates viral gene expression by inducing the phosphorylation of the C-terminal domain (CTD) of RNA Pol II through several Tat-activated kinases and by recruiting chromatin remodeling complexes and histone modifying enzymes to the HIV-1 LTR. Histone acetyl-transferases (HATs), including p300 and hGCN5, not only acetylate histones but also acetylate Tat at lysine positions 50 and 51 in the arginine-rich motif (ARM). Acetylated Tat (AcTat) at positions 50 and 51 interacts with a specialized protein module, the bromodomain, and recruits novel factors having this particular domain such as P/CAF and SWI/SNF. Other than its effect on transcription, Tat has been shown to be involved in splicing. In this study, we demonstrate that Tat interacts with CDK13 both in vivo and in vitro. We also found that CDK13 increases HIV-1 mRNA splicing and favours the production of the doubly-spliced protein Nef. In addition, we demonstrate that CDK13 acts as a possible restriction factor, in that its overexpression decreases the production of the viral proteins Gag and Env and subsequently suppresses virus production. Using siRNA against CDK13, we show that silencing of CDK13 leads to a significant increase in virus production. Finally, we demonstrate that CDK13 mediates its effect on splicing through the phosphorylation of ASF/SF2. 10.1128/JVI.02543-07 JF - J. Virol. TI - CDK13: A NEW POTENTIAL HIV-1 INHIBITORY FACTOR REGULATING VIRAL mRNA SPLICING SP - JVI.02543-07 KW - aids KW - asfsf2 KW - cdc2-related KW - cdc2l5 KW - cdk13 KW - ched KW - cycl KW - cyclin KW - cyclin-l KW - factor KW - hiv KW - kinase KW - mrna KW - restriction KW - sea KW - splicing KW - tat KW - transactivation KW - urchin KW - virus AU - Berro, Reem AU - Pedati, Caitlin AU - Kehn-Hall, Kylene AU - Wu, Weilin AU - Klase, Zachary AU - Even, Yasmine AU - Geneviere, Anne-Marie AU - Ammosova, Tatiana AU - Nekhai, Sergei AU - Kashanchi, Fatah PY - 2008/05/14/ UR - http://dx.doi.org/10.1128/JVI.02543-07 ER -