Document Detail

In several cell types tumour suppressor p53 induces apoptosis largely via Puma but Noxa can contribute.
MedLine Citation:
PMID:  18259198     Owner:  NLM     Status:  MEDLINE    
The ability of p53 to induce apoptosis in cells with damaged DNA is thought to contribute greatly to its tumour suppressor function. P53 has been proposed to induce apoptosis via numerous transcriptional targets or even by direct cytoplasmic action. Two transcriptional targets shown to mediate its apoptotic role in several cell types encode Noxa and Puma, BH3-only members of the Bcl-2 family. To test if their functions in p53-dependent apoptosis overlap, we generated mice lacking both. These mice develop normally and no tumours have yet arisen. In embryonic fibroblasts, the absence of both Noxa and Puma prevented induction of apoptosis by etoposide. Moreover, following whole body gamma-irradiation, the loss of both proteins protected thymocytes better than loss of Puma alone. Indeed, their combined deficiency protected thymocytes as strongly as loss of p53 itself. These results indicate that, at least in fibroblasts and thymocytes, p53-induced apoptosis proceeds principally via Noxa and Puma, with Puma having the predominant role in diverse cell types. The absence of tumours in the mice suggests that tumour suppression by p53 requires functions in addition to induction of apoptosis.
E M Michalak; A Villunger; J M Adams; A Strasser
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-02-08
Journal Detail:
Title:  Cell death and differentiation     Volume:  15     ISSN:  1350-9047     ISO Abbreviation:  Cell Death Differ.     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-05-19     Completed Date:  2008-07-28     Revised Date:  2014-09-11    
Medline Journal Info:
Nlm Unique ID:  9437445     Medline TA:  Cell Death Differ     Country:  England    
Other Details:
Languages:  eng     Pagination:  1019-29     Citation Subset:  IM    
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MeSH Terms
Adenovirus E1A Proteins / metabolism
Apoptosis Regulatory Proteins
Cell Transformation, Viral
Etoposide / toxicity
Fibroblasts / drug effects,  virology
Gamma Rays
Lymphocytes / drug effects
Mice, Inbred C57BL
Mice, Knockout
Neoplasms, Experimental / etiology
Proto-Oncogene Proteins c-bcl-2 / genetics,  physiology*
Thymus Gland / cytology,  radiation effects
Tumor Suppressor Protein p53 / genetics,  metabolism*
Tumor Suppressor Proteins / genetics,  physiology*
Grant Support
CA043540-18/CA/NCI NIH HHS; CA80188-6/CA/NCI NIH HHS; R01 CA043540/CA/NCI NIH HHS; R01 CA043540-18/CA/NCI NIH HHS; R01 CA080188-06/CA/NCI NIH HHS; Y 212-B12//Austrian Science Fund FWF
Reg. No./Substance:
0/Adenovirus E1A Proteins; 0/Apoptosis Regulatory Proteins; 0/PUMA protein, mouse; 0/Pmaip1 protein, mouse; 0/Proto-Oncogene Proteins c-bcl-2; 0/Tumor Suppressor Protein p53; 0/Tumor Suppressor Proteins; 6PLQ3CP4P3/Etoposide

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