Functional interplay between p53 and E2F through co-activator p300

Oncogene
C W LeeN B La Thangue

Abstract

Both E2F and p53 are sequence specific transcription factors that regulate early cell cycle progression. The pathway of control mediated through E2F governs the transition from G1 into S phase whereas p53 in response to genotoxic stress can facilitate cell cycle arrest or apoptosis. The mechanisms which influence the outcome of p53 induction are not clear, although transcription of the p53 target gene, encoding the cdk-inhibitor p21(Waf1/Cip1), correlates with p53-mediated cell cycle arrest. Here using a combination of biochemical and functional assays we identify p300 as a co-activator required for p53-dependent transcriptional activation of Waf1/Cip1. Furthermore, we show that the cdk-inhibitor p21(Waf1/Cip1) autoregulates in a positive fashion transcription through modulating the activity of the p53/p300 complex, whilst negatively regulating the activity of E2F by preventing cdk-dependent phosphorylation of pRb. Consistent with a role for p21(Waf1/Cip1) in the autoregulation of p53-dependent transcription, p300 augments the ability of p53 to cause G1 arrest and, conversely, cells undergoing p53-dependent apoptosis are rescued by p300. Thus, our data suggest that the ability of p300 to interact with p53 influences the physiol...Continue Reading

Citations

Sep 25, 1999·Journal of Cellular Physiology·A Giordano, M L Avantaggiati
May 22, 2002·Biochimica Et Biophysica Acta·James DeGregori
Sep 18, 2001·European Journal of Biochemistry·M KoziczakY Nagamine
Aug 13, 2011·The Journal of Biological Chemistry·Li-Hsin SuChin-Hung Sun
Feb 10, 2004·Molecular Biology of the Cell·Bernat Baeza-Raja, Pura Muñoz-Cánoves
Feb 25, 2000·Molecular and Cellular Biology·O Loughran, N B La Thangue
Mar 25, 2000·Molecular and Cellular Biology·A W SnowdenN D Perkins
Apr 25, 2002·Molecular and Cellular Biology·Gerardo FerbeyreScott W Lowe
Jun 5, 2012·American Journal of Physiology. Lung Cellular and Molecular Physiology·Yong-Chul Kim, Regina M Day
May 5, 2004·Proceedings of the National Academy of Sciences of the United States of America·N Gopalakrishna IyerCarlos Caldas
Jul 18, 2002·Proceedings of the National Academy of Sciences of the United States of America·James L CookJay R Radke
Jan 17, 2015·Chemical Reviews·Beverley M Dancy, Philip A Cole
May 4, 2005·Biochemical and Biophysical Research Communications·Amanda S Coutts, Nicholas B La Thangue
Apr 7, 2012·Biochemical and Biophysical Research Communications·Yukari YoshiharaToshinori Ozaki
Jul 31, 2012·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Jung-Ae KimKeon Wook Kang
Aug 21, 2001·Molecular Cell·C DemonacosN B La Thangue
Oct 13, 1999·Molecular Cell·N ShikamaN B La Thangue
Sep 28, 1999·Oncogene·L Delavaine, N B La Thangue
Feb 22, 2002·Oncogene·Rhonda CroxtonW Douglas Cress

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