Human inhibitor of apoptosis proteins: why XIAP is the black sheep of the family
Human inhibitor of apoptosis proteins: why XIAP is the black sheep of the family
复制标题
DOI：
10.1038/sj.embor.7400795
复制
发表时间：
2006-10-01
期刊：
影响因子：
7.7
通讯作者：
Scott, Fiona L.
中科院分区：
文献类型：
--
作者：
Eckelman, Brendan P.;Salvesen, Guy S.;Scott, Fiona L.
凋亡抑制蛋白（IAP）家族成员中的几个调节细胞凋亡，以响应各种细胞攻击。一些成员还参与细胞信号传导、有丝分裂和将蛋白质靶向到泛素-蛋白酶体降解机制。最深入研究的家族成员，X-连锁IAP（XIAP），是一种有效的半胱天冬酶活性抑制剂，因此，通常认为直接半胱天冬酶抑制是该家族大多数成员的重要保守功能。生物化学和结构研究已经精确地绘制了半胱天冬酶抑制所需的XIAP元件。有趣的是，这些元素在IAP中并不保守。在这里，我们回顾了目前的知识的caspase抑制潜力的人类IAP和显示，XIAP可能是唯一真正的caspase抑制剂，这表明其他家庭成员从来没有获得直接抑制caspase活性的能力。
Several of the inhibitor of apoptosis protein (IAP) family members regulate apoptosis in response to various cellular assaults. Some members are also involved in cell signalling, mitosis and targeting proteins to the ubiquitin-proteasome degradation machinery. The most intensively studied family member, X-linked IAP ( XIAP), is a potent inhibitor of caspase activity; hence, it is generally assumed that direct caspase inhibition is an important conserved function of most members of the family. Biochemical and structural studies have precisely mapped the elements of XIAP required for caspase inhibition. Intriguingly, these elements are not conserved among IAPs. Here, we review current knowledge of the caspase-inhibitory potential of the human IAPs and show that XIAP is probably the only bona fide caspase inhibitor, suggesting that the other family members never gained the ability to directly inhibit caspase activity.