Yang Y L, Li X M
Laboratory of Immune Cell Biology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Cell Res. 2000 Sep;10(3):169-77. doi: 10.1038/sj.cr.7290046.
IAPs (inhibitors of apoptosis) are a family of proteins containing one or more characteristic BIR domains. These proteins have multiple biological activities that include binding and inhibiting caspases, regulating cell cycle progression, and modulating receptor-mediated signal transduction. Our recent studies found the IAP family members XIAP and c-IAP1 are ubiquitinated and degraded in proteasomes in response to apoptotic stimuli in T cells, and their degradation appears to be important for T cells to commit to death. In addition to three BIR domains, each of these IAPs also contains a RING finger domain. We found this region confers ubiquitin protease ligase (E3) activity to IAPs, and is responsible for the auto-ubiquitination and degradation of IAPs after an apoptotic stimulus. Given the fact that IAPs can bind a variety of proteins, such as caspases and TRAFs, it will be of interest to characterize potential substrates of the E3 activity of IAPs and the effects of ubiquitination by IAPs on signal transduction, cell cycle, and apoptosis.
凋亡抑制蛋白（IAPs）是一类含有一个或多个特征性BIR结构域的蛋白质家族。这些蛋白质具有多种生物学活性，包括结合并抑制半胱天冬酶、调节细胞周期进程以及调节受体介导的信号转导。我们最近的研究发现，IAP家族成员XIAP和c-IAP1在T细胞中响应凋亡刺激时会在蛋白酶体中发生泛素化并降解，它们的降解似乎对T细胞走向死亡很重要。除了三个BIR结构域之外，这些IAP中的每一个还含有一个指环结构域。我们发现该区域赋予IAP泛素蛋白酶连接酶（E3）活性，并负责凋亡刺激后IAP的自身泛素化和降解。鉴于IAP能够结合多种蛋白质，如半胱天冬酶和TRAFs，鉴定IAP E3活性的潜在底物以及IAP介导的泛素化对信号转导、细胞周期和凋亡的影响将很有意义。
