The phosphorylation of Metaxin 1 controls Bak activation during TNFα induced cell death

The phosphorylation of Metaxin 1 controls Bak activation during TNFα induced cell death
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DOI:
10.1016/j.cellsig.2016.11.008
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发表时间:
2017-01-01
影响因子:
4.8
通讯作者:
Vallette, Francois M.
Vallette, Francois M.
中科院分区:
生物学2区
文献类型:
--
作者:
Petit, Elise;Cartron, Pierre-Francois;Vallette, Francois M.

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促凋亡蛋白Bak参与细胞凋亡的执行阶段,这是一种细胞死亡程序。Bak本质上是线粒体,在凋亡的早期阶段经历构象变化,导致其在线粒体中的全膜整合和随后的促凋亡线粒体蛋白的释放。我们对Bak激活的伙伴和机制知之甚少。我们最近的研究表明,在静止和死亡细胞中,Bak被纳入2型(VDAC2)/Metaxin 1(Mtx1)/Metaxin 2 (Mtx2)多蛋白复合物的电压依赖性阴离子通道中。在这里,我们表明,在诱导凋亡后,Bak从与Mtx2和VDAC2的关联切换到与Mtx1的更紧密的关联。这种伴侣的改变是由c-Abl对Mtx1的酪氨酸磷酸化控制的。(C) 2016 Elsevier Inc.版权所有。
The proapoptotic protein Bak is implicated in the execution phase of apoptosis, a cell death program. Bak is essentially mitochondrial and during early steps of apoptosis undergoes conformational changes that lead to its full membrane integration in mitochondria and the subsequent liberation of pro-apoptotic mitochondria( proteins. Little is known about the partners and mechanisms implicated in the activation of Bak. We have recently shown that Bak is incorporated into a Voltage dependent anionic channel of type 2 (VDAC2)/Metaxin 1(Mtx1)/Metaxin 2 (Mtx2) multi-protein complex in both resting and dying cells. Here, we show that, after the induction of apoptosis, Bak switches from its association with Mtx2 and VDAC2 to a closer association with Mtx1. This change of partners is under the control of a tyrosine phosphorylation of Mtx1 by c-Abl. (C) 2016 Elsevier Inc. All rights reserved.