Excess HDM2 impacts cell cycle and apoptosis and has a selective effect on p53-dependent transcription.

The Journal of Biological Chemistry
Shuichi OhkuboCarol Prives

Abstract

Mutational inactivation of p53 is only one of the ways that tumors lose p53 function. An alternate route is through overexpression of HDM2, the negative regulator of p53. To further understand how excess HDM2 regulates p53-mediated functions, we generated H1299 cell clones that constitutively express both ectopic HDM2 and tetracycline-regulated inducible p53. We found that over a range of p53 concentrations constitutively expressed HDM2 did not affect the levels of p53 protein. Nevertheless, cells with excess HDM2 displayed numerous changes in their response to p53. After DNA damage, such cells had both increased p53-mediated G2 arrest and reduced cell death. They also showed selective impairment of p53 target gene induction in that some p53 targets were unaffected whereas others were markedly less well induced in the presence of extra HDM2 protein. We also found that excess HDM2 was correlated with reduced p53 acetylation but did not affect p53 association with target promoters in vivo. Indeed, there was no significant difference in the amount of HDM2 associated with p53 at target promoters that differed in their expression depending on the presence of extra HDM2. Thus, HDM2 can selectively down-regulate the transcription func...Continue Reading

References

May 1, 1987·Somatic Cell and Molecular Genetics·L Cahilly-SnyderD L George
Jul 1, 1993·Molecular and Cellular Biology·J ChenA J Levine
Jul 1, 1993·Genes & Development·X WuA J Levine
May 1, 1996·Molecular and Cellular Biology·J ChenA J Levine
May 15, 1997·Nature·Y HauptM Oren
May 15, 1997·Nature·M H KubbutatK H Vousden
Aug 1, 1997·Genes & Development·C J ThutR Tjian
Sep 26, 1997·Nature·K PolyakB Vogelstein
May 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·H LuA J Levine
Jul 11, 1998·Molecular Cell·H HermekingB Vogelstein
Sep 23, 1998·Genes & Development·K SakaguchiE Appella
Oct 9, 1998·Genes & Development·A J Giaccia, M B Kastan
Nov 20, 1998·Molecular and Cellular Biology·D A Freedman, A J Levine
Mar 31, 1999·Proceedings of the National Academy of Sciences of the United States of America·X W WangC C Harris
May 26, 1999·The Journal of Pathology·C Prives, P A Hall
Jan 5, 2000·Oncogene·M Ashcroft, K H Vousden
Mar 18, 2000·The Journal of Biological Chemistry·S FangA M Weissman
Aug 10, 2000·The Journal of Biological Chemistry·R OhkiT Taniguchi
Sep 12, 2000·Nature Cell Biology·S D BoydT Jacks
Sep 12, 2000·Nature Cell Biology·R K GeyerC G Maki
Nov 9, 2000·Proceedings of the National Academy of Sciences of the United States of America·E KobetH Lu
Dec 1, 2000·Nature·B VogelsteinA J Levine
Apr 21, 2001·Molecular and Cellular Biology·S T SzakJ A Pietenpol
May 19, 2001·European Journal of Biochemistry·E Appella, C W Anderson
Nov 20, 2001·Molecular and Cellular Biology·M A LohrumK H Vousden
Jan 10, 2002·Cell·C Prives, J L Manley
Mar 29, 2002·Nature Genetics·Ana ContenteMatthias Dobbelstein
Apr 18, 2002·Oncogene·Seiichi NakamuraTapas Mukhopadhyay
May 2, 2002·Molecular Cell·Koji OkamotoCarol Prives
Jun 18, 2002·The Journal of Biological Chemistry·Yetao JinHua Lu
Nov 12, 2002·The EMBO Journal·Akihiro ItoTso-Pang Yao

❮ Previous
Next ❯

Citations

Mar 2, 2013·Cell Death and Differentiation·M Farhang GhahremaniJ J Haigh
Apr 21, 2010·Cell Research·Christopher L Brooks, Wei Gu
Dec 2, 2008·Nature Reviews. Drug Discovery·Alexei VazquezGareth L Bond
Jul 20, 2010·Nature Structural & Molecular Biology·Masha V PoyurovskyCarol Prives
Oct 29, 2009·The Journal of Biological Chemistry·Tomohiro NishimuraKyoko Tsukiyama-Kohara
May 15, 2007·The Journal of Biological Chemistry·Christopher L BrooksWei Gu
Aug 4, 2010·Cold Spring Harbor Perspectives in Biology·Rachel Beckerman, Carol Prives
Mar 21, 2007·Molecular and Cellular Biology·Luciana E Giono, James J Manfredi
Nov 15, 2012·Genes & Cancer·Lynn BidermanCarol Prives
Jun 1, 2011·FEBS Letters·Christopher L Brooks, Wei Gu
Aug 31, 2014·Clinica Chimica Acta; International Journal of Clinical Chemistry·Chuck C-K Chao
Sep 21, 2011·Molecular and Cellular Endocrinology·Jonathan D WassermanDavid Malkin
Oct 12, 2010·Trends in Molecular Medicine·Chao Dai, Wei Gu
Mar 24, 2009·Journal of Molecular Biology·Lakshminarasimhan PavithraSamit Chattopadhyay
May 29, 2009·Mutation Research·Soumya ChatterjeeArindam Bhattacharyya
Nov 29, 2014·The Journal of Investigative Dermatology·Anil SebastianArdeshir Bayat
Feb 26, 2008·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Li-Je ChenGuor Mour Her
Feb 8, 2011·The EMBO Journal·Takao KurodaJunn Yanagisawa
May 20, 2009·Cell·Jan-Philipp Kruse, Wei Gu
May 5, 2009·Cell·Karen H Vousden, Carol Prives
May 20, 2008·Cell·Yi TangWei Gu
Oct 22, 2016·Molecular Carcinogenesis·Wing-Po ChakKa-Fai To
Nov 11, 2017·Cell Death and Differentiation·Kelly D SullivanJoaquin M Espinosa
Mar 24, 2010·The Journal of Biological Chemistry·Hongxia XuRuiwen Zhang
Feb 17, 2021·The FEBS Journal·Laura Friedel, Alexander Loewer
Jan 1, 2018·Cell Death and Differentiation·Kelly D SullivanJoaquin M Espinosa

❮ 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

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.