Warnakulasuriyarachchi Dinesh, Cerquozzi Sonia, Cheung Herman H, Holcík Martin
Apoptosis Research Center, Children's Hospital of Eastern Ontario, Department of Pediatrics, University of Ottawa, Ottawa, Ontario K1H 8L1, Canada.
J Biol Chem. 2004 Apr 23;279(17):17148-57. doi: 10.1074/jbc.M308737200. Epub 2004 Feb 11.
Prolonged endoplasmic reticulum (ER) stress leads to activation of caspases and cell death. The inhibitor of apoptosis (IAP) proteins are intrinsic inhibitors of apoptosis by virtue of inhibiting distinct caspases and are, therefore, critical regulators of cell death. Here we demonstrate that the expression of one member of the IAP family, HIAP2, is induced in response to ER stress and attenuates ER stress-induced cell death. The induction of HIAP2 is executed at the level of protein synthesis and is mediated by an inducible internal ribosome entry site (IRES) element. The triggering of ER stress results in caspase-mediated proteolytic processing of eukaryotic initiation factor p97/DAP5/NAT1, producing a fragment that specifically activates HIAP2 IRES. These data suggest an existence of a novel mechanism that regulates apoptotic response in ER stress.
内质网（ER）应激延长会导致半胱天冬酶激活和细胞死亡。凋亡抑制蛋白（IAP）家族凭借抑制不同的半胱天冬酶而成为细胞凋亡的内在抑制剂，因此是细胞死亡的关键调节因子。在此我们证明，IAP家族的一个成员HIAP2的表达在ER应激反应中被诱导，并减弱ER应激诱导的细胞死亡。HIAP2的诱导在蛋白质合成水平上进行，并由一个可诱导的内部核糖体进入位点（IRES）元件介导。ER应激的触发导致真核起始因子p97/DAP5/NAT1的半胱天冬酶介导的蛋白水解加工，产生一个特异性激活HIAP2 IRES的片段。这些数据表明存在一种调节ER应激中凋亡反应的新机制。
