Gene-specific requirement for P-TEFb activity and RNA polymerase II phosphorylation within the p53 transcriptional program

Genes & Development
Nathan P GomesJoaquin M Espinosa

Abstract

Activation of the p53 pathway mediates cellular responses to diverse forms of stress. Here we report that the p53 target gene p21(CIP1) is regulated by stress at post-initiation steps through conversion of paused RNA polymerase II (RNAP II) into an elongating form. High-resolution chromatin immunoprecipitation assays (ChIP) demonstrate that p53-dependent activation of p21(CIP1) transcription after DNA damage occurs concomitantly with changes in RNAP II phosphorylation status and recruitment of the elongation factors DSIF (DRB Sensitivity-Inducing Factor), P-TEFb (Positive Transcription Elongation Factor b), TFIIH, TFIIF, and FACT (Facilitates Chromatin Transcription) to distinct regions of the p21(CIP1) locus. Paradoxically, pharmacological inhibition of P-TEFb leads to global inhibition of mRNA synthesis but activation of the p53 pathway through p53 accumulation, expression of specific p53 target genes, and p53-dependent apoptosis. ChIP analyses of p21(CIP1) activation in the absence of functional P-TEFb reveals the existence of two distinct kinases that phosphorylate Ser5 of the RNAP II C-terminal domain (CTD). Importantly, CTD phosphorylation at Ser2 is not required for p21(CIP1) transcription, mRNA cleavage, or polyadenylat...Continue Reading

References

Jul 2, 1992·Nature·G FarmerC Prives
Jun 21, 1991·Science·S E KernB Vogelstein
Nov 19, 1993·Cell·W S el-DeiryB Vogelstein
Oct 25, 1996·The Journal of Biological Chemistry·N F MarshallD H Price
Apr 18, 1998·The Journal of Biological Chemistry·S TrigonM Morange
Jun 5, 1999·Microbiology and Molecular Biology Reviews : MMBR·J D Richter
Mar 25, 2000·Molecular and Cellular Biology·D H Price
Dec 1, 2000·Nature·B VogelsteinA J Levine
Mar 30, 2001·The Journal of Biological Chemistry·Y RamanathanT Pe'ery
Jun 30, 2001·The Journal of Biological Chemistry·S H Chao, D H Price
Mar 23, 2002·Cell·Nick J ProudfootMichael J Dye
Apr 19, 2002·Biochimica Et Biophysica Acta·Karen H Vousden
Aug 3, 2002·Nature Reviews. Cancer·Karen H Vousden, Xin Lu
Sep 6, 2002·Biochimica Et Biophysica Acta·Michael S Kobor, Jack Greenblatt
Dec 31, 2002·Molecular Cell·Pantelis Hatzis, Iannis Talianidis
May 2, 2003·The Journal of Biological Chemistry·Michele YeoGordon N Gill
May 24, 2003·The Journal of Biological Chemistry·Mark Gerber, Ali Shilatifard
Nov 5, 2003·Progress in Cell Cycle Research·Peter M FischerLaurent Meijer
Jan 24, 2004·The EMBO Journal·Minkyu KimStephen Buratowski
Mar 30, 2004·The Journal of Biological Chemistry·Janice C JonesArno L Greenleaf
May 6, 2004·Molecular Cell·Shankarling KrishnamurthyMichael Hampsey
Oct 19, 2004·Genes & Development·Robert J SimsDanny Reinberg
Jan 6, 2005·Molecular and Cellular Biology·Tiaojiang XiaoBrian D Strahl
May 20, 2005·Current Opinion in Cell Biology·David L Bentley
Jul 26, 2005·The Journal of Biological Chemistry·Todd E AdamsonDavid H Price
Sep 10, 2005·Science·Jerry E ChipukDouglas R Green

❮ Previous
Next ❯

Citations

Apr 21, 2011·Apoptosis : an International Journal on Programmed Cell Death·Xènia Garrofé-OchoaJacint Boix
Oct 13, 2009·Nature Structural & Molecular Biology·Jarnail Singh, Richard A Padgett
Jan 26, 2010·Nature Structural & Molecular Biology·Aaron J DonnerJoaquín M Espinosa
May 11, 2010·Nature Structural & Molecular Biology·Krista D MeyerDylan J Taatjes
Jun 22, 2010·Nature Structural & Molecular Biology·Iván D'Orso, Alan D Frankel
Aug 31, 2010·Nature Structural & Molecular Biology·Joshua R TietjenAseem Z Ansari
Oct 16, 2012·Nature Structural & Molecular Biology·Stéphane LarochelleRobert P Fisher
Dec 25, 2007·Nature Structural & Molecular Biology·Kira Glover-CutterDavid L Bentley
Aug 29, 2007·Oncogene·S K RadhakrishnanA L Gartel
Nov 2, 2012·Proceedings of the National Academy of Sciences of the United States of America·Jayasha ShandilyaStefan G E Roberts
Dec 26, 2012·Proceedings of the National Academy of Sciences of the United States of America·Renier Vélez-CruzJean-Marc Egly
Jul 16, 2013·Proceedings of the National Academy of Sciences of the United States of America·Thomas CherrierOlivier Rohr
Oct 8, 2011·The Journal of Biological Chemistry·Jessica Finlay-SchultzSherry Leonard
Jul 25, 2012·The Journal of Biological Chemistry·Federico PelischAnabella Srebrow
Jan 29, 2008·The Journal of Biological Chemistry·Kazuki MochizukiKeiko Ozato
Oct 12, 2010·Molecular Human Reproduction·Zhen Zhen ZhaoGrant W Montgomery
Mar 20, 2009·Nucleic Acids Research·Ian R LoganCraig N Robson
Aug 4, 2010·Cold Spring Harbor Perspectives in Biology·Rachel Beckerman, Carol Prives
May 3, 2007·Genes & Development·Xiaoling WangJ Peter Gergen
Aug 3, 2007·Genes & Development·Nicolas GévryLuc Gaudreau
Dec 31, 2009·Genes & Development·José M MorachisBeverly M Emerson
May 19, 2010·Genes & Development·Nathan P Gomes, Joaquín M Espinosa
Jan 19, 2010·Genes & Development·Nathan P Gomes, Joaquín M Espinosa
Sep 29, 2012·Genes & Development·Corrie L Gallant-BehmJoaquín M Espinosa
Apr 5, 2011·Genes & Development·Yupeng ChenKatherine A Jones
Dec 18, 2010·Genome Research·Joanna Y IpBenjamin J Blencowe
Jul 28, 2006·Cold Spring Harbor Symposia on Quantitative Biology·D P Lane
Aug 9, 2011·The Journal of Pharmacology and Experimental Therapeutics·Fabiola Cervantes-GomezVarsha Gandhi
May 20, 2009·Molecular and Cellular Biology·Sylvain EgloffShona Murphy
May 16, 2007·Molecular and Cellular Biology·Liat Amir-ZilbersteinRivka Dikstein
Aug 22, 2007·Molecular and Cellular Biology·Charlotte BarrandonOlivier Bensaude
Nov 14, 2007·Molecular and Cellular Biology·Alexandra C RacanelliRichard G Moran

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis