Proteolytic cleavage of human p53 by calpain: a potential regulator of protein stability.

Molecular and Cellular Biology
M H Kubbutat, K H Vousden

Abstract

The p53 tumor suppressor protein is activated in cells in response to DNA damage and prevents the replication of cells sustaining genetic damage by inducing a cell cycle arrest or apoptosis. Activation of p53 is accompanied by stabilization of the protein, resulting in accumulation to high levels within the cell. p53 is normally degraded through the proteasome following ubiquitination, although the mechanisms which regulate this proteolysis in normal cells and how the p53 protein becomes stabilized following DNA damage are not well understood. We show here that p53 can also be a substrate for cleavage by the calcium-activated neutral protease, calpain, and that a preferential site for calpain cleavage exists within the N terminus of the p53 protein. Treatment of cells expressing wild-type p53 with an inhibitor of calpain resulted in the stabilization of the p53 protein. By contrast, in vitro or in vivo degradation mediated by human papillomavirus E6 protein was unaffected by the calpain inhibitor, indicating that the stabilization did not result from inhibition of the proteasome. These results suggest that calpain cleavage plays a role in regulating p53 stability.

References

May 29, 1992·Cell·A Varshavsky
Aug 1, 1992·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·D E GollT Zalewska
Jun 1, 1992·Molecular and Cellular Biology·W D FunkJ W Shay
Jun 21, 1991·Science·S E KernB Vogelstein
Jul 1, 1991·Physiological Reviews·D E Croall, G N DeMartino
Feb 1, 1987·Molecular and Cellular Biology·G J MatlashewskiL V Crawford
Sep 1, 1984·Molecular and Cellular Biology·W Maltzman, L Czyzyk
Sep 25, 1995·Biochemical and Biophysical Research Communications·W ZhuC Y Young
Sep 1, 1995·Genes & Development·Y HauptM Oren
Sep 1, 1995·Genes & Development·P SabbatiniE White
Aug 29, 1995·Proceedings of the National Academy of Sciences of the United States of America·P AtadjaK Riabowol
Mar 3, 1995·Science·S M CrossB J Reid
Jan 1, 1994·Current Biology : CB·T JacksR A Weinberg
Mar 1, 1994·Molecular and Cellular Biology·D R ChowdaryH L Ozer
Mar 15, 1994·Proceedings of the National Academy of Sciences of the United States of America·J A PietenpolB Vogelstein
May 1, 1994·Journal of Cellular Physiology·M K SquìerJ J Cohen
Nov 11, 1993·Nucleic Acids Research·F Watt, P L Molloy
Jul 1, 1993·Molecular and Cellular Biology·Q ZhanA J Fornace
Jul 1, 1993·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·G P Zambetti, A J Levine
May 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·T D KessisK R Cho
Jan 1, 1996·The Biochemical Journal·S CarilloM Piechaczyk
Mar 22, 1996·Science·K FukasawaG F Vande Woude
May 1, 1996·Molecular and Cellular Biology·J ChenA J Levine
Feb 1, 1996·Current Opinion in Genetics & Development·S Bates, K H Vousden

❮ Previous
Next ❯

Citations

May 29, 2004·FEBS Letters·Josephine E Sutcliffe, Alexander Brehm
Apr 30, 2014·The Journal of Cell Biology·Cortney C WinkleStephanie L Gupton
May 13, 2014·Biochimica Et Biophysica Acta·Yinan Hua, Sreejayan Nair
Oct 23, 2015·Circulation Journal : Official Journal of the Japanese Circulation Society·Brittany A PotzFrank W Sellke
Apr 8, 2004·Neoplasia : an International Journal for Oncology Research·N O CarragherM C Frame
Aug 10, 2000·Neoplasia : an International Journal for Oncology Research·M Ljungman
May 29, 2004·The Plant Journal : for Cell and Molecular Biology·Joon-Woo AhnHyun-Sook Pai
Jan 25, 2008·International Journal of Cancer. Journal International Du Cancer·Lei LiuXuejuan Gao
Feb 17, 2006·Biology of the Cell·Lauréline RogerPierre Roux
Mar 5, 2014·The American Journal of Pathology·Guodong LianFei Ye
Jun 30, 2000·Molecular Genetics and Metabolism·A Grimberg
Jul 10, 2004·Experimental Cell Research·Insook KimYoung Soo Ahn
Jul 10, 2004·Experimental Cell Research·F RaynaudY Benyamin
Mar 10, 2001·Experimental Cell Research·D B Woods, K H Vousden
Mar 26, 2004·Biochemical Pharmacology·Judit JánossyPeter Friedrich
Jan 30, 2008·Biophysical Journal·Jin Hyoung KimKyu-Won Kim
Jun 23, 2009·BMC Cardiovascular Disorders·Isabel GonçalvesIsabella Pörn-Ares
Jun 29, 2007·Molecular and Cellular Neurosciences·Eun Jung LeeKwang Chul Chung
Nov 11, 2014·Journal of Medicinal Chemistry·Yosup RewSteven H Olson
Jun 25, 2005·Biochemical and Biophysical Research Communications·Eliana MunarrizPierluigi Nicotera
Nov 16, 2013·PloS One·Shuai GaoLirim Shemshedini
Jun 27, 2014·Journal of Medicinal Chemistry·Yosup Rew, Daqing Sun
Sep 24, 1999·Journal of Neuroscience Research·S L Chan, M P Mattson
Aug 29, 2003·The American Journal of Chinese Medicine·Jung-Chou ChenKuei-Chu Chen
Jun 22, 2007·Proceedings of the National Academy of Sciences of the United States of America·Berna S SayanGerry Melino

❮ 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