Pin1-Induced Proline Isomerization in Cytosolic p53 Mediates BAX Activation and Apoptosis.
Pin1-Induced Proline Isomerization in Cytosolic p53 Mediates BAX Activation and Apoptosis.
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DOI：
10.1016/j.molcel.2015.06.029
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发表时间：
2015-08-20
期刊：
影响因子：
16
通讯作者：
Kriwacki RW
中科院分区：
文献类型：
--
作者：
Follis AV;Llambi F;Merritt P;Chipuk JE;Green DR;Kriwacki RW
肿瘤抑制因子p53的胞质部分激活凋亡效应蛋白BAX以触发凋亡。在这里，我们报告说，p53激活BAX通过不同的机制与激活BH 3蛋白（BIM和BID）。我们观察到，顺-反异构化的脯氨酸47（Pro47）内p53，一个固有的罕见的分子事件，是必需的BAX激活。脯氨酰异构酶Pin 1通过催化p53 Pro 47的顺-反相互转化增强p53依赖的BAX活化。我们的研究结果揭示了一个信号机制，其中脯氨酸顺反异构化在一个蛋白质触发下游信号合作伙伴的构象和功能的变化。通过胞质p53和Pin 1的协同作用激活BAX可能整合细胞应激信号以诱导直接的凋亡反应。
The cytosolic fraction of the tumor suppressor p53 activates the apoptotic effector protein BAX to trigger apoptosis. Here we report that p53 activates BAX through a mechanism different from that associated with activation by BH3 only proteins (BIM and BID). We observed that cis-trans isomerization of proline 47 (Pro47) within p53, an inherently rare molecular event, was required for BAX activation. The prolyl isomerase Pin1 enhanced p53-dependent BAX activation by catalyzing cis-trans interconversion of p53 Pro47. Our results reveal a signaling mechanism whereby proline cis-trans isomerization in one protein triggers conformational and functional changes in a downstream signaling partner. Activation of BAX through the concerted action of cytosolic p53 and Pin1 may integrate cell stress signals to induce a direct apoptotic response.