PUMA couples the nuclear and cytoplasmic proapoptotic function of p53
PUMA couples the nuclear and cytoplasmic proapoptotic function of p53
复制标题
DOI：
10.1126/science.1114297
复制
发表时间：
2005-09-09
期刊：
影响因子：
56.9
通讯作者：
Green, DR
中科院分区：
文献类型：
--
作者：
Chipuk, JE;Bouchier-Hayes, L;Green, DR
Trp53肿瘤抑制基因产物（tumor suppressor gene product, p53）在细胞核中调控促凋亡基因，而细胞质中的p53则直接激活促凋亡的Bcl-2蛋白，使线粒体通透化，引发细胞凋亡。在这里，我们证明了Bcl-xL、细胞质p53和PUMA之间的三方联系协调了这些不同的p53功能。基因毒性应激后，Bcl-xL可隔离细胞质p53。核p53引起PUMA的表达，PUMA随后将p53从Bcl-xL中移出，使p53诱导线粒体通透性。突变体Bcl-xL结合p53，但不结合PUMA，使细胞抵抗p53诱导的凋亡，而不考虑PUMA的表达。因此，PUMA结合了p53的细胞核和细胞质促凋亡功能。
The Trp53 tumor suppressor gene product (p53) functions in the nucleus to regulate proapoptotic genes, whereas cytoplasmic p53 directly activates proapoptotic Bcl-2 proteins to permeabilize mitochondria and initiate apoptosis. Here, we demonstrate that a tripartite nexus between Bcl-xL, cytoplasmic p53, and PUMA coordinates these distinct p53 functions. After genotoxic stress, Bcl-xL sequestered cytoplasmic p53. Nuclear p53 caused expression of PUMA, which then displaced p53 from Bcl-xL, allowing p53 to induce mitochondria) permeabilization. Mutant Bcl-xL that bound p53, but not PUMA, rendered cells resistant to p53-induced apoptosis irrespective of PUMA expression. Thus, PUMA couples the nuclear and cytoplasmic proapoptotic functions of p53.