线粒体膜间蛋白Smac和卵巢癌

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Smac是存在于线粒体并调节细胞凋亡的蛋白质,其促凋亡作用是通过逆转凋亡抑制蛋白(IAPs)尤其是X连锁凋亡抑制蛋白(XIAP)的作用实现的。当细胞受到凋亡刺激时,线粒体释放Smac蛋白到细胞质中,后者与IAPs结合,使其丧失抑制半胱氨酸天冬氨酸蛋白酶(caspase)活性的作用,从而促进细胞凋亡。细胞凋亡的减少与肿瘤的发生关系密切,认为Smac蛋白分别是caspase凋亡依赖途径和非caspase凋亡依赖途径的组成部分,其结构、功能、释放及调节成为研究热点。通过调控凋亡信号转导途径相关的胞内调控因子可能影响肿瘤细胞的化疗敏感性,因此Smac在卵巢肿瘤耐药性机制中的作用也受到关注。 Smac is a protein that exists in mitochondria and regulates apoptosis, and its proapoptotic effect is mediated by the reversal of apoptosis-inhibiting proteins (IAPs), especially X-linked inhibitor of apoptosis (XIAP). When cells are stimulated by apoptosis, mitochondria release Smac protein into the cytoplasm, which, in combination with IAPs, loses the effect of inhibiting caspase activity and thus promotes apoptosis. The decrease of apoptosis is closely related to the occurrence of tumor. Smac protein is considered as an integral part of caspase-dependent apoptosis pathway and non-caspase-dependent pathway, respectively. Its structure, function, release and regulation have become the hot topics. The role of Smac in the mechanism of drug resistance in ovarian cancer has drawn attention as well, through the regulation of intracellular regulators related to apoptotic signal transduction pathways that may influence the chemosensitivity of tumor cells.
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