PUMA, a novel proapoptotic gene, is induced by p53
PUMA, a novel proapoptotic gene, is induced by p53
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DOI：
10.1016/s1097-2765(01)00214-3
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发表时间：
2001-03-01
期刊：
影响因子：
16
通讯作者：
Vousden, KH
中科院分区：
文献类型：
--
作者：
Nakano, K;Vousden, KH
p53 肿瘤抑制蛋白起到转录激活剂的作用，并且已经描述了在响应 p53 诱导细胞凋亡中发挥作用的几种 p53 诱导基因。我们已经鉴定出一种名为 PUMA（p53 上调细胞凋亡调节剂）的新基因，作为 p53 激活的靶标。该基因编码两种包含 BH3 结构域的蛋白质（PUMA-α 和 PUMA-β），这些蛋白质在 p53 激活后在细胞中被诱导。 PUMA-a(和PUMA-P表现出相似的活性；它们与Bcl-2结合，定位于线粒体诱导细胞色素c释放，并激活程序性细胞死亡的快速诱导。PUMA表达的反义抑制减少了对p53的凋亡反应，PUMA很可能通过细胞色素c/Apaf-1依赖性介导p53诱导的细胞死亡。 途径。
The p53 tumor-suppressor protein functions as a transcriptional activator, and several p53-inducible genes that play a role in the induction of apoptosis in response to p53 have been described. We have identified a novel gene named PUMA (p53 upregulated modulator of apoptosis) as a target for activation by p53. This gene encodes two BH3 domain-containing proteins (PUMA-alpha and PUMA-beta) that are induced in cells following p53 activation. PUMA-a( and PUMA-P show similar activities; they bind to Bcl-2, localize to the mitochondria to induce cytochrome c release, and activate the rapid induction of programmed cell death. Antisense inhibition of PUMA expression reduced the apoptotic response to p53, and PUMA is likely to play a role in mediating p53-induced cell death through the cytochrome c/Apaf-1-dependent pathway.