Wellcome Centre for Cell-Matrix Research, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
Division of Cancer Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
Cell Death Dis. 2020 Oct 16;11(10):872. doi: 10.1038/s41419-020-03091-8.
Apoptotic priming controls the commitment of cells to apoptosis by determining how close they lie to mitochondrial permeabilisation. Variations in priming are important for how both healthy and cancer cells respond to chemotherapeutic agents, but how it is dynamically coordinated by Bcl-2 proteins remains unclear. The Bcl-2 family protein Bid is phosphorylated when cells enter mitosis, increasing apoptotic priming and sensitivity to antimitotic drugs. Here, we report an unbiased proximity biotinylation (BioID) screen to identify regulators of apoptotic priming in mitosis, using Bid as bait. The screen primarily identified proteins outside of the canonical Bid interactome. Specifically, we found that voltage-dependent anion-selective channel protein 2 (VDAC2) was required for Bid phosphorylation-dependent changes in apoptotic priming during mitosis. These results highlight the importance of the wider Bcl-2 family interactome in regulating the temporal control of apoptotic priming.
凋亡引发控制细胞向凋亡的定向，其决定因素是细胞与线粒体通透化的接近程度。引发的变化对于健康细胞和癌细胞对化疗药物的反应都很重要，但 Bcl-2 蛋白如何动态协调这一过程仍不清楚。当细胞进入有丝分裂时，Bcl-2 家族蛋白 Bid 被磷酸化，增加凋亡引发和对抗有丝分裂药物的敏感性。在这里，我们使用 Bid 作为诱饵，报告了一种无偏的邻近生物素化 (BioID) 筛选方法，以鉴定有丝分裂中凋亡引发的调节剂。该筛选主要鉴定了经典 Bid 相互作用组之外的蛋白。具体来说，我们发现电压依赖性阴离子选择性通道蛋白 2 (VDAC2) 在有丝分裂期间 Bid 磷酸化依赖性凋亡引发变化中是必需的。这些结果强调了更广泛的 Bcl-2 家族相互作用组在调节凋亡引发的时间控制中的重要性。
