Wu Hao, Tschopp Jurg, Lin Su-Chang
Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021, USA.
Cell. 2007 Nov 16;131(4):655-8. doi: 10.1016/j.cell.2007.10.042.
Inhibitor of apoptosis proteins (IAPs) such as XIAP, cIAP1, and cIAP2 are upregulated in many cancer cells. It has been thought that small-molecule mimetics of Smac, an endogenous IAP antagonist, might potentiate apoptosis in cancer cells by promoting caspase activation. However, three recent papers, two in Cell (Vince et al., 2007; Varfolomeev et al., 2007) and one in Cancer Cell (Petersen et al., 2007), now report that Smac mimetics primarily kill cancer cells via a different mechanism, the induction of autoubiquitination and degradation of cIAPs, which culminates in TNFalpha-mediated cell death.
凋亡抑制蛋白（IAPs），如X连锁凋亡抑制蛋白（XIAP）、细胞凋亡抑制蛋白1（cIAP1）和细胞凋亡抑制蛋白2（cIAP2），在许多癌细胞中上调。人们一直认为，内源性IAP拮抗剂Smac的小分子模拟物可能通过促进半胱天冬酶激活来增强癌细胞的凋亡。然而，最近有三篇论文，两篇发表在《细胞》杂志上（文斯等人，2007年；瓦尔福洛梅耶夫等人，2007年），一篇发表在《癌细胞》杂志上（彼得森等人，2007年），现在报道Smac模拟物主要通过一种不同的机制杀死癌细胞，即诱导cIAPs的自身泛素化和降解，最终导致肿瘤坏死因子α（TNFα）介导的细胞死亡。
