title: UBC9-dependent association between calnexin and protein tyrosine phosphatase 1B (PTP1B) at the endoplasmic reticulum.
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.
authors.affiliation: From the Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada and.
authors.forename: Dukgyu
authors.initials: D
authors.lastname: Lee
authors.affiliation: From the Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada and.
authors.forename: Allison
authors.initials: A
authors.lastname: Kraus
authors.affiliation: From the Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada and.
authors.forename: Daniel
authors.initials: D
authors.lastname: Prins
authors.affiliation: From the Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada and.
authors.forename: Jody
authors.initials: J
authors.lastname: Groenendyk
authors.affiliation: McGill Cancer Centre, Department of Biochemistry, McGill University, Montreal, Quebec H3G 1Y6, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Aubry
authors.affiliation: From the Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada and.
authors.forename: Wen-Xin
authors.initials: WX
authors.lastname: Liu
authors.affiliation: From the Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada and.
authors.forename: Hao-Dong
authors.initials: HD
authors.lastname: Li
authors.affiliation: From the Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada and.
authors.forename: Olivier
authors.initials: O
authors.lastname: Julien
authors.affiliation: From the Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada and.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Touret
authors.affiliation: From the Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada and.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Sykes
authors.affiliation: McGill Cancer Centre, Department of Biochemistry, McGill University, Montreal, Quebec H3G 1Y6, Canada.
authors.forename: Michel L
authors.initials: ML
authors.lastname: Tremblay
authors.affiliation: McGill Cancer Centre, Department of Biochemistry, McGill University, Montreal, Quebec H3G 1Y6, Canada marek.michalak@ualberta.ca.
authors.forename: Marek
authors.initials: M
authors.lastname: Michalak
mesh_terms: D000818:Animals; D015153:Blotting, Western; D037281:Calnexin / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D041681:NIH 3T3 Cells; D011485:Protein Binding; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D058207:Sumoylation; D020798:Two-Hybrid System Techniques; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism*; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: D037281:Calnexin; D044763:Ubiquitin-Conjugating Enzymes; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D000098843:Ubiquitin-Conjugating Enzyme UBC9
keywords: chaperone; endoplasmic reticulum (ER); protein folding; small ubiquitin-like modifier (SUMO); tyrosine-protein phosphatase (tyrosine phosphatase)