UBC9-dependent Association between Calnexin and Protein Tyrosine Phosphatase 1B (PTP1B) at the Endoplasmic Reticulum |
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| Authors: | Dukgyu Lee Allison Kraus Daniel Prins Jody Groenendyk Isabelle Aubry Wen-Xin Liu Hao-Dong Li Olivier Julien Nicolas Touret Brian D. Sykes Michel L. Tremblay Marek Michalak |
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| Affiliation: | 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 |
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| Abstract: | 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. |
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| Keywords: | chaperone endoplasmic reticulum (ER) protein folding small ubiquitin-like modifier (SUMO) tyrosine-protein phosphatase (tyrosine phosphatase) |
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