p53- and drug-induced apoptotic responses mediated by BH3-only proteins Puma and Noxa
Details
Publication Year 2003-11-07, Volume 302, Issue #5647, Page 1036-1038
Journal Title
SCIENCE
Publication Type
Journal Article
Abstract
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.
Publisher
AMER ASSOC ADVANCEMENT SCIENCE
Keywords
COLORECTAL-CANCER CELLS; BCL-2 FAMILY; DNA-DAMAGE; P53; DEATH; GENE; THYMOCYTES; EXPRESSION; INDUCTION; SURVIVAL
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2003-11-07 12:00:00
Last Modified: 0001-01-01 12:00:00
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