PMID: 9649502Jul 3, 1998Paper

Suppression of the p300-dependent mdm2 negative-feedback loop induces the p53 apoptotic function

Genes & Development
A Thomas, E White

Abstract

The p53 tumor suppressor gene product interacts with the p300 transcriptional coactivator that regulates the transactivation of p53-inducible genes. The adenovirus E1A protein has been shown to bind to p300 and inhibit its function. E1A inhibits p53 transactivation and also promotes p53 accumulation by a p300-dependent mechanism. Murine double minute 2 (Mdm2) is a transcriptional target of p53 that binds to p53 and inhibits its transcriptional activity. E1A inhibited mdm2 transactivation without affecting the expression of p21(WAF1) or Bax, which resulted in high levels of p53 accumulation and apoptosis. Ectopic expression of p300 restored Mdm2 levels and inhibited p53-dependent apoptosis, as did ectopic expression of Mdm2. Thus, p300 is required for mdm2 induction by p53 and the subsequent inhibition of p53 stabilization. Inhibition of p300 by E1A results in stabilization of p53 and causes apoptosis. Moreover, E1B 19K or Bcl-2 expression in E1A-transformed cells abrogated p53-dependent apoptosis by restoring mdm2 transactivation by p53. Hence, p300 regulation of mdm2 expression controls apoptotic activity of p53, and 19K or Bcl-2 bypass E1A inhibition of p300 transactivation of Mdm2.

References

Apr 1, 1992·Nature Genetics·W S el-DeiryB Vogelstein
Aug 21, 1992·Cell·B Vogelstein, K W Kinzler
Jul 5, 1991·Science·M HollsteinC C Harris
Sep 1, 1995·Genes & Development·P SabbatiniE White
Oct 1, 1993·Proceedings of the Society for Experimental Biology and Medicine·E White
Sep 13, 1994·Proceedings of the National Academy of Sciences of the United States of America·Y Shen, T Shenk
Mar 15, 1994·Proceedings of the National Academy of Sciences of the United States of America·J A PietenpolB Vogelstein
Apr 1, 1994·Molecular and Cellular Biology·S K ChiouE White
Nov 19, 1993·Cell·W S el-DeiryB Vogelstein
Jul 1, 1993·Genes & Development·X WuA J Levine
Apr 1, 1993·Genes & Development·M Debbas, E White
Oct 28, 1993·Nature·J C ChriviaR H Goodman
Feb 1, 1993·Current Opinion in Genetics & Development·E Moran
Jan 1, 1996·Genes & Development·E White
Mar 1, 1996·Genes & Development·P DaiS Ishii
May 1, 1996·Molecular and Cellular Biology·W T SteegengaA G Jochemsen
May 1, 1996·Molecular and Cellular Biology·J ChenA J Levine
May 1, 1996·Genes & Development·L J Ko, C Prives
Dec 19, 1996·Nature·A J Bannister, T Kouzarides
Dec 1, 1996·The Journal of Cell Biology·L RaoE White
Feb 1, 1997·Current Opinion in Genetics & Development·L Rao, E White
May 15, 1997·Nature·Y HauptM Oren

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Citations

Sep 25, 1999·Journal of Cellular Physiology·A Giordano, M L Avantaggiati
Aug 10, 1999·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·M V Blagosklonny
Apr 8, 2000·Trends in Cell Biology·M A Lohrum, K H Vousden
Apr 18, 2000·Mutation Research·M S ColmanJ C Barrett
May 19, 2001·European Journal of Biochemistry·S R Grossman
May 5, 2004·Proceedings of the National Academy of Sciences of the United States of America·N Gopalakrishna IyerCarlos Caldas
Mar 23, 2002·Leukemia & Lymphoma·Roger K StrairDaniel J Medina
Feb 21, 2004·Biochemical and Biophysical Research Communications·Teruhisa KawamuraToru Kita
Jan 17, 2012·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Yasumoto YamasakiToshiyoshi Fujiwara
Oct 13, 1999·Molecular Cell·N ShikamaN B La Thangue
Nov 11, 1998·Molecular Cell·S R GrossmanD M Livingston
Nov 22, 2005·Oncogene·Clodagh C O'Shea
Jan 5, 2000·Oncogene·M Ashcroft, K H Vousden
Aug 20, 2002·Oncogene·Kerri A DuganMichael D Cole
Dec 17, 2002·Oncogene·Madhavi KadakiaSteven J Berberich
Apr 21, 2001·Cell Death and Differentiation·F J GeskeL E Gerschenson
Dec 11, 2019·FEBS Letters·Wing Hang Ip, Thomas Dobner
Oct 12, 2000·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·M V Blagosklonny
Nov 26, 1998·The Journal of Biological Chemistry·P F LambertJ N Brady
Mar 20, 1999·The Journal of Biological Chemistry·R V SionovY Haupt
Dec 18, 2003·The Journal of Biological Chemistry·Hongtae KimYoung-Pil Wang
Dec 9, 2003·The Journal of Biological Chemistry·Francesca ManciniFabiola Moretti
Mar 3, 2005·The Journal of Biological Chemistry·Andrew V SamuelsonScott W Lowe
Jan 18, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Mary Helen Barcellos-Hoff
Oct 9, 1998·Genes & Development·C J Sherr

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