Document Detail

Proteolytic cleavage of human p53 by calpain: a potential regulator of protein stability.
MedLine Citation:
PMID:  8972227     Owner:  NLM     Status:  MEDLINE    
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.
M H Kubbutat; K H Vousden
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular and cellular biology     Volume:  17     ISSN:  0270-7306     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  1997 Jan 
Date Detail:
Created Date:  1997-01-22     Completed Date:  1997-01-22     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  460-8     Citation Subset:  IM    
ABL Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702, USA.
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MeSH Terms
Adenosine Triphosphate / analogs & derivatives,  pharmacology
Adenylyl Imidodiphosphate / pharmacology
Amino Acid Sequence
Breast Neoplasms
Calpain / antagonists & inhibitors,  metabolism*
Chelating Agents / pharmacology
Cysteine Proteinase Inhibitors / pharmacology
Edetic Acid / pharmacology
Molecular Sequence Data
Oncogene Proteins, Viral / metabolism
Repressor Proteins*
Tumor Cells, Cultured
Tumor Suppressor Protein p53 / genetics,  metabolism*
Reg. No./Substance:
0/Chelating Agents; 0/Cysteine Proteinase Inhibitors; 0/E6 protein, Human papillomavirus type 16; 0/Oncogene Proteins, Viral; 0/Repressor Proteins; 0/Tumor Suppressor Protein p53; 25612-73-1/Adenylyl Imidodiphosphate; 35094-46-3/adenosine 5'-O-(3-thiotriphosphate); 56-65-5/Adenosine Triphosphate; 60-00-4/Edetic Acid; EC 3.4.22.-/Calpain

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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