夏普
凋亡抑制因子
泛素连接酶
泛素
半胱氨酸蛋白酶
细胞凋亡
半胱氨酸蛋白酶-9
细胞生物学
无名指
化学
半胱氨酸蛋白酶3
激活剂(遗传学)
无名指区
生物
分子生物学
生物化学
锌指
程序性细胞死亡
受体
转录因子
基因
作者
Y. Morizane,Reiko Honda,Kiyoko Fukami,Hideyo Yasuda
摘要
Members of the IAP (inhibitor of apoptosis) family function as anti-apoptotic proteins by binding directly to caspase-3, -7, and -9 to inhibit their activities. During apoptosis, the activities of IAPs are relieved by a second mitochondria-derived caspase activator, named Smac/DIABLO. Some IAPs have a C-terminal RING finger domain that has been identified as the essential motif for the activity of ubiquitin ligase (E3). Here we show that X-linked IAP (XIAP) mediates the polyubiquitination of caspase-9 and Smac. The large subunit of mature caspase-9 was polyubiquitinated by XIAP in vitro, while procaspase-9 was not. Furthermore, the polyubiquitinated form of caspase-9 accumulated in an XIAP-dependent manner in intact cells. The ubiquitination of caspase-9 was significantly inhibited in the presence of mature Smac, whereas XIAP was also found to promote the polyubiquitination of cytosolic Smac both in vitro and in intact cells. These ubiquitination reactions require the RING finger domain of XIAP. These findings suggest that XIAP functions as ubiquitin ligase toward mature caspase-9 and Smac to inhibit apoptosis.
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