Puma is an essential mediator of p53-dependent and -independent apoptotic pathways
Puma is an essential mediator of p53-dependent and -independent apoptotic pathways
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DOI：
10.1016/s1535-6108(03)00244-7
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发表时间：
2003-10-01
期刊：
影响因子：
50.3
通讯作者：
Zambetti, GP
中科院分区：
文献类型：
--
作者：
Jeffers, JR;Parganas, E;Zambetti, GP
Puma编码由p53肿瘤抑制因子和其他凋亡刺激物诱导的仅BH 3蛋白。为了评估其在细胞凋亡中的生理作用，我们通过基因打靶产生了Puma敲除小鼠。在这里，我们报告说，彪马是必不可少的造血细胞死亡触发电离辐射（IR），失调的c-Myc表达，细胞因子撤退。Puma也是整个发育中的神经系统中IR诱导的死亡所必需的，并且在这些条件下几乎所有归因于p53的凋亡活性都是Puma引起的。这些发现确立了Puma作为响应于不同凋亡信号的细胞死亡的主要介质，暗示Puma作为可能的肿瘤抑制剂。
Puma encodes a BH3-only protein that is induced by the p53 tumor suppressor and other apoptotic stimuli. To assess its physiological role in apoptosis, we generated Puma knockout mice by gene targeting. Here we report that Puma is essential for hematopoietic cell death triggered by ionizing radiation (IR), deregulated c-Myc expression, and cytokine withdrawal. Puma is also required for IR-induced death throughout the developing nervous system and accounts for nearly all of the apoptotic activity attributed to p53 under these conditions. These findings establish Puma as a principal mediator of cell death in response to diverse apoptotic signals, implicating Puma as a likely tumor suppressor.