凋亡抑制蛋白XIAP研究进展

Research Progress of the Inhibitor-of-protein XIAP

X连锁凋亡抑制蛋白(XIAP)是哺乳动物中具有抑制细胞凋亡作用的蛋白,是IAPs家族的一员。XIAP通过杆状病毒IAP重复序列(BIR)直接与起始以及效应caspases结合,抑制了细胞凋亡的线粒体途径,也可以通过NF-kB途径抑制细胞表面受体介导的凋亡。XIAP具有不同于Bcl-2的作用机制,是IAPs家族中最具有抑制活性的一个。XIAP的作用受到线粒体释放的蛋白Smac的拮抗,以及受到自身具有泛素连接酶E3活性的RING指结构域的调节。阐述XIAP抑制caspase以及Smac等拮抗XIAP的机理对于治疗肿瘤以及过度凋亡疾病具有重要的意义。

XIAP is a mammalian inhibitor of apoptosis protein, which belongs to the inhibitor-of-apoptosis protein(IAP)family. XIAP is a potent suppressor of apoptotic cell death. The BIR domain of XIAP binds directly to certain initiator and effector caspases,thus blocks the mitochondria death pathway. XIAP also can be as a acti-tor of NF -κB pathway and inhibit caspase - 8. This differs the effects of Bel - 2 - related apoptotic suppressors, which function at points that are distal in the death pathway, upstearm of the apoptosome, to prevent integration of the caspase-activating signal. Smac is a mitochondria protein that is released along with cytochrome c during apoptosis abd protome cytochrome-dependent caspase activation by neutralizing XIAP. The RING finger domain of XIAP has the activity of ubiquititin protein ligase E3 and can cause the auto - ubiquitination and degradaton of XIAP,and regulate the activation of XIAP.