Lee Dukgyu, Kraus Allison, Prins Daniel, Groenendyk Jody, Aubry Isabelle, Liu Wen-Xin, Li Hao-Dong, Julien Olivier, Touret Nicolas, Sykes Brian D, Tremblay Michel L, Michalak Marek
From the Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada and.
McGill Cancer Centre, Department of Biochemistry, McGill University, Montreal, Quebec H3G 1Y6, Canada.
J Biol Chem. 2015 Feb 27;290(9):5725-38. doi: 10.1074/jbc.M114.635474. Epub 2015 Jan 13.
Calnexin is a type I integral endoplasmic reticulum (ER) membrane protein, molecular chaperone, and a component of the translocon. We discovered a novel interaction between the calnexin cytoplasmic domain and UBC9, a SUMOylation E2 ligase, which modified the calnexin cytoplasmic domain by the addition of SUMO. We demonstrated that calnexin interaction with the SUMOylation machinery modulates an interaction with protein tyrosine phosphatase 1B (PTP1B), an ER-associated protein tyrosine phosphatase involved in the negative regulation of insulin and leptin signaling. We showed that calnexin and PTP1B form UBC9-dependent complexes, revealing a previously unrecognized contribution of calnexin to the retention of PTP1B at the ER membrane. This work shows that the SUMOylation machinery links two ER proteins from divergent pathways to potentially affect cellular protein quality control and energy metabolism.
钙连接蛋白是一种I型内质网（ER）整合膜蛋白、分子伴侣和转位子的一个组成部分。我们发现了钙连接蛋白胞质结构域与UBC9（一种SUMO化E2连接酶）之间的新型相互作用，UBC9通过添加SUMO修饰钙连接蛋白胞质结构域。我们证明，钙连接蛋白与SUMO化机制的相互作用调节了与蛋白酪氨酸磷酸酶1B（PTP1B）的相互作用，PTP1B是一种与内质网相关的蛋白酪氨酸磷酸酶，参与胰岛素和瘦素信号的负调控。我们表明，钙连接蛋白和PTP1B形成依赖UBC9的复合物，揭示了钙连接蛋白对PTP1B在内质网膜上保留的先前未被认识的作用。这项工作表明，SUMO化机制将来自不同途径的两种内质网蛋白联系起来，可能影响细胞蛋白质质量控制和能量代谢。
