Publication Date:
2003-09-23
Description:
Apoptosis provoked by DNA damage requires the p53 tumor suppressor, but which of the many p53-regulated genes are required has remained unknown. Two genes induced by this transcription factor, noxa and puma (bbc3), stand out, because they encode BH3-only proteins, proapoptotic members of the Bcl-2 family required to initiate apoptosis. In mice with either noxa or puma disrupted, we observed decreased DNA damage-induced apoptosis in fibroblasts, although only loss of Puma protected lymphocytes from cell death. Puma deficiency also protected cells against diverse p53-independent cytotoxic insults, including cytokine deprivation and exposure to glucocorticoids, the kinase inhibitor staurosporine, or phorbol ester. Hence, Puma and Noxa are critical mediators of the apoptotic responses induced by p53 and other agents.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Villunger, Andreas -- Michalak, Ewa M -- Coultas, Leigh -- Mullauer, Franziska -- Bock, Gunther -- Ausserlechner, Michael J -- Adams, Jerry M -- Strasser, Andreas -- New York, N.Y. -- Science. 2003 Nov 7;302(5647):1036-8. Epub 2003 Sep 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia. andreas.villunger@uibk.ac.at〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14500851" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
*Apoptosis
;
Apoptosis Regulatory Proteins
;
B-Lymphocytes/drug effects/physiology
;
Cell Transformation, Viral
;
Cytokines/physiology
;
DNA Damage
;
Dexamethasone/pharmacology
;
Etoposide/pharmacology
;
Fibroblasts/drug effects/*physiology
;
Gamma Rays
;
Gene Targeting
;
Ionomycin/pharmacology
;
Lymphocytes/drug effects/*physiology
;
Mice
;
Mice, Inbred C57BL
;
Mice, Knockout
;
Models, Biological
;
Proto-Oncogene Proteins/genetics/*physiology
;
Proto-Oncogene Proteins c-bcl-2/genetics/*physiology
;
RNA, Messenger/genetics/metabolism
;
Reverse Transcriptase Polymerase Chain Reaction
;
T-Lymphocytes/drug effects/physiology
;
Tetradecanoylphorbol Acetate/pharmacology
;
Transcription, Genetic
;
Tumor Suppressor Protein p53/genetics/*physiology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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