Santelli Eugenio, Leone Marilisa, Li Chenlong, Fukushima Toru, Preece Nicholas E, Olson Arthur J, Ely Kathryn R, Reed John C, Pellecchia Maurizio, Liddington Robert C, Matsuzawa Shu-ichi
The Burnham Institute, La Jolla, California 92037, USA.
J Biol Chem. 2005 Oct 7;280(40):34278-87. doi: 10.1074/jbc.M506707200. Epub 2005 Aug 4.
Siah1 is the central component of a multiprotein E3 ubiquitin ligase complex that targets beta-catenin for destruction in response to p53 activation. The E3 complex comprises, in addition to Siah1, Siah-interacting protein (SIP), the adaptor protein Skp1, and the F-box protein Ebi. Here we show that SIP engages Siah1 by means of two elements, both of which are required for mediating beta-catenin destruction in cells. An N-terminal dimerization domain of SIP sits across the saddle-shaped upper surface of Siah1, with two extended legs packing against the sides of Siah1 by means of a consensus PXAXVXP motif that is common to a family of Siah-binding proteins. The C-terminal domain of SIP, which binds to Skp1, protrudes from the lower surface of Siah1, and we propose that this surface provides the scaffold for bringing substrate and the E2 enzyme into apposition in the functional complex.
Siah1是一种多蛋白E3泛素连接酶复合物的核心成分，该复合物在p53激活时靶向β-连环蛋白进行降解。除Siah1外，E3复合物还包括Siah相互作用蛋白（SIP）、衔接蛋白Skp1和F-box蛋白Ebi。我们在此表明，SIP通过两个元件与Siah1结合，这两个元件对于介导细胞中β-连环蛋白的降解都是必需的。SIP的N端二聚化结构域位于Siah1鞍形上表面，两条延伸的臂通过Siah结合蛋白家族共有的一致PXAXVXP基序靠在Siah1的侧面。SIP与Skp1结合的C端结构域从Siah1下表面突出，我们推测该表面为在功能复合物中将底物和E2酶并列提供了支架。
