p53's mitochondrial translocation and MOMP action is independent of Puma and Bax and severely disrupts mitochondrial membrane integrity.
p53's mitochondrial translocation and MOMP action is independent of Puma and Bax and severely disrupts mitochondrial membrane integrity.
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P53的凋亡程序包括转录依赖性和转录非依赖性途径。在后者中，线粒体p53与线粒体通透性调节因子Bcl2家族的抗凋亡和促凋亡成员之间的物理相互作用是核心。使用具有明确缺陷的等基因细胞系统，我们详细描述了线粒体p53如何促进线粒体通透性，其作用在多大程度上依赖于其他关键Bcl2家族成员，并定义了其释放活性。我们发现，线粒体p53通过严重破坏线粒体内外膜的完整性，高效地诱导可溶性和不可溶性凋亡因子的释放。这种作用与野生型p53诱导的Bax、Bak和VDAC的寡聚化以及p53和亲环蛋白D之间应力诱导的内源性复合物的形成有关，该复合物通常位于内膜。肿瘤来源的p53突变体缺乏激活Bax/Bak脂质孔。这些行动独立于Puma和Bax。重要的是，后者区分了线粒体和细胞质p53死亡途径。
p53's apoptotic program consists of transcription-dependent and transcription-independent pathways. In the latter, physical interactions between mitochondrial p53 and anti- and pro-apoptotic members of the Bcl2 family of mitochondrial permeability regulators are central. Using isogenic cell systems with defined deficiencies, we characterize in detail how mitochondrial p53 contributes to mitochondrial permeabilization, to what extent its action depends on other key Bcl2 family members and define its release activity. We show that mitochondrial p53 is highly efficient in inducing the release of soluble and insoluble apoptogenic factors by severely disrupting outer and inner mitochondrial membrane integrity. This action is associated with wild-type p53-induced oligomerization of Bax, Bak and VDAC and the formation of a stress-induced endogenous complex between p53 and cyclophilin D, normally located at the inner membrane. Tumor-derived p53 mutants are deficient in activating the Bax/Bak lipid pore. These actions are independent of Puma and Bax. Importantly, the latter distinguishes the mitochondrial from the cytosolic p53 death pathway.
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影响因子：
64.5
作者：
Du, CY;Fang, M;Wang, XD
通讯作者：
Wang, XD
DOI：
10.1073/pnas.94.8.3668
发表时间：
1997-04-15
影响因子：
11.1
作者：
Hsu, YT;Wolter, KG;Youle, RJ
通讯作者：
Youle, RJ
影响因子：
4.3
作者：
Erster, S;Moll, UM
通讯作者：
Moll, UM
影响因子：
5.3
作者：
Endo, Hidenori;Kamada, Hiroshi;Chan, Pak H.
通讯作者：
Chan, Pak H.
影响因子：
3.9
作者：
Endo, H.;Saito, A.;Chan, P. H.
通讯作者：
Chan, P. H.