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Publication : p53- and drug-induced apoptotic responses mediated by BH3-only proteins puma and noxa.

First Author  Villunger A Year  2003
Journal  Science Volume  302
Issue  5647 Pages  1036-8
PubMed ID  14500851 Mgi Jnum  J:86466
Mgi Id  MGI:2679929 Doi  10.1126/science.1090072
Citation  Villunger A, et al. (2003) p53- and drug-induced apoptotic responses mediated by BH3-only proteins puma and noxa. Science 302(5647):1036-8
abstractText  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.
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