Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA.
Mol Cell. 2011 Jan 7;41(1):107-16. doi: 10.1016/j.molcel.2010.12.002. Epub 2010 Dec 23.
ARTS (apoptosis-related protein in the TGF-β signaling pathway) is a mitochondrial protein that binds XIAP (X-linked inhibitor of apoptosis protein) upon entering the cytosol, thus promoting cell death. Expression of ARTS is lost in some malignancies. Here, we show that ARTS binds to XIAP at BIR1, a domain distinct from the caspase-binding sites. Furthermore, ARTS interacts with the E3 ligase Siah-1 (seven in absentia homolog 1) to induce ubiquitination and degradation of XIAP. Cells lacking either Siah or ARTS contain higher steady-state levels of XIAP. Thus, ARTS serves as an adaptor to bridge Siah-1 to XIAP, targeting it for destruction.
ARTS(转化生长因子-β信号通路中的凋亡相关蛋白)是一种线粒体蛋白,当进入细胞质时与 XIAP(凋亡抑制蛋白 X 连锁)结合,从而促进细胞死亡。在某些恶性肿瘤中,ARTS 的表达丢失。在这里,我们表明 ARTS 在 BIR1 与 XIAP 结合,BIR1 是一个与 caspase 结合位点不同的结构域。此外,ARTS 与 E3 连接酶 Siah-1(七个缺失同源物 1)相互作用,诱导 XIAP 的泛素化和降解。缺乏 Siah 或 ARTS 的细胞含有更高的 XIAP 稳定状态水平。因此,ARTS 作为衔接蛋白将 Siah-1 桥接到 XIAP 上,将其靶向破坏。