The anti-apoptotic protein Mcl-1 inhibits mitochondrial Ca2+ signals
The anti-apoptotic protein Mcl-1 inhibits mitochondrial Ca2+ signals
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DOI：
10.1074/jbc.m503210200
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发表时间：
2005-09-30
影响因子：
4.8
通讯作者：
Nathanson, MH
中科院分区：
文献类型：
--
作者：
Minagawa, N;Kruglov, EA;Nathanson, MH
细胞凋亡有助于调节细胞的生长和再生，并促进肿瘤的发展。MCL-1是一种抗细胞凋亡蛋白，在血液和胆道恶性肿瘤的发生发展过程中起着重要的作用，但其作用机制尚不清楚。许多促凋亡和抗凋亡蛋白通过调节钙信号而发挥作用，因此我们研究了Mcl-1对钙信号通路中已知的调节细胞凋亡的成分的影响。Mcl-1的表达不影响肌醇1，4，5-三磷酸受体的表达，也不影响内质网钙库的大小。然而，在高表达Mcl-1的细胞中，由钙激动剂或凋亡刺激诱导的线粒体Ca~(2+)信号减少，而在Mcl-1表达被抑制的细胞中，线粒体钙信号增加。这些发现为Mcl-1直接抑制线粒体内的钙信号提供了证据，这可能提供了一种新的机制来抑制细胞凋亡，从而促进肿瘤的发生。
Apoptosis contributes to the regulation of cell growth and regeneration and to the development of neoplasia. Mcl-1 is an anti-apoptotic protein that is particularly important for the development of hematological and biliary malignancies, but the mechanism of action of Mcl-1 is unknown. A number of pro- and anti-apoptotic proteins exhibit their effects by modulating Ca2+ signals, so we examined the effects of Mcl-1 on components of the Ca2+ signaling pathway that are known to regulate apoptosis. Expression of Mcl-1 did not affect expression of the inositol 1,4,5-trisphosphate receptor or the size of endoplasmic reticulum Ca2+ stores. However, mitochondrial Ca2+ signals induced by either Ca2+ agonists or apoptotic stimuli were decreased in cells overexpressing Mcl-1 and increased in cells in which Mcl-1 expression was inhibited. These findings provide evidence that Mcl-1 directly inhibits Ca2+ signals within mitochondria, which may provide a novel mechanism to inhibit apoptosis and thereby promote neoplasia.