Document Detail

Paradoxical suppression of cellular senescence by p53.
MedLine Citation:
PMID:  20457898     Owner:  NLM     Status:  MEDLINE    
The tumor suppressor p53 is a canonical inducer of cellular senescence (irreversible loss of proliferative potential and senescent morphology). p53 can also cause reversible arrest without senescent morphology, which has usually been interpreted as failure of p53 to induce senescence. Here we demonstrate that p53-induced quiescence actually results from suppression of senescence by p53. In previous studies, suppression of senescence by p53 was masked by p53-induced cell cycle arrest. Here, we separated these two activities by inducing senescence through overexpression of p21 and then testing the effect of p53 on senescence. We found that in p21-arrested cells, p53 converted senescence into quiescence. Suppression of senescence by p53 required its transactivation function. Like rapamycin, which is known to suppress senescence, p53 inhibited the mTOR pathway. We suggest that, while inducing cell cycle arrest, p53 may simultaneously suppress the senescence program, thus causing quiescence and that suppression of senescence and induction of cell cycle arrest are distinct functions of p53. Thus, in spite of its ability to induce cell cycle arrest, p53 can act as a suppressor of cellular senescence.
Zoya N Demidenko; Lioubov G Korotchkina; Andrei V Gudkov; Mikhail V Blagosklonny
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-05-10
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  107     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-26     Completed Date:  2010-06-29     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  9660-4     Citation Subset:  IM    
Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
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MeSH Terms
Cell Aging* / drug effects
Cell Line, Tumor
Imidazoles / pharmacology
Intracellular Signaling Peptides and Proteins / metabolism
Piperazines / pharmacology
Protein-Serine-Threonine Kinases / metabolism
Signal Transduction
TOR Serine-Threonine Kinases
Transcriptional Activation
Tumor Suppressor Protein p53 / genetics,  metabolism*
Grant Support
Reg. No./Substance:
0/Imidazoles; 0/Intracellular Signaling Peptides and Proteins; 0/Piperazines; 0/TP53 protein, human; 0/Tumor Suppressor Protein p53; 0/nutlin 3; EC protein, human; EC Serine-Threonine Kinases; EC Kinases

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