p53- and drug-induced apoptotic responses mediated by BH3-only proteins Puma and Noxa
p53- and drug-induced apoptotic responses mediated by BH3-only proteins Puma and Noxa
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DOI：
10.1126/science.1090072
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发表时间：
2003-11-07
期刊：
影响因子：
56.9
通讯作者：
Strasser, A
中科院分区：
文献类型：
--
作者：
Villunger, A;Michalak, EM;Strasser, A
由DNA损伤引起的细胞凋亡需要p53肿瘤抑制因子，但是需要许多p53调节基因中的哪一个仍然未知。由该转录因子诱导的两个基因noxa和puma（bbc 3）脱颖而出，因为它们编码仅BH 3蛋白，Bcl-2家族的促凋亡成员需要启动细胞凋亡。在noxa或puma破坏的小鼠中，我们观察到成纤维细胞中DNA损伤诱导的凋亡减少，尽管只有Puma的损失保护淋巴细胞免于细胞死亡。Puma缺陷还保护细胞免受各种p53非依赖性细胞毒性损伤，包括细胞因子剥夺和暴露于糖皮质激素、激酶抑制剂星形孢菌素或佛波酯。因此，Puma和Noxa是由p53和其他试剂诱导的凋亡反应的关键介质。
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.