title: SUMOylation of GPS2 protein regulates its transcription-suppressing function.
abstract: G-protein pathway suppressor 2 (GPS2) is a human suppressor of G protein-activated mitogen-activated protein kinase signaling. It is involved in many physiological processes, including DNA repair, cell proliferation, apoptosis, and brain development. In this study, we show that GPS2 can be modified by the small ubiquitin-like modifier (SUMO) SUMO-1 but not SUMO-2 or -3. Two SUMOylation sites (K45 and K71) are identified in the N-terminal coiled-coil domain of GPS2. Substitution of K45 with arginine reduces SUMOylation, whereas substitution of K71 or both K45 and K71 with arginine abolishes SUMOylation, with more of the double mutant GPS2 appearing in the cytosol than in the nucleus compared with wild type and the two-single-mutant GPS2. SUMOylation stabilizes GPS2 protein by promoting its interaction with TBL1 and reducing its ubiquitination. SUMOylation also enhances the ability of GPS2 to suppress transcription and promotes its ability to inhibit estrogen receptor α-mediated transcription by increasing its association with SMRT, as demonstrated in MCF-7 and T47D cells. Moreover, SUMOylation of GPS2 also represses the proliferation of MCF-7 and T47D cells. These findings suggest that posttranslational modification of GPS2 by SUMOylation may serve as a key factor that regulates the function of GPS2 in vivo.
authors.affiliation: School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024, China.
authors.forename: Hailian
authors.initials: H
authors.lastname: Bi
authors.affiliation: School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024, China.
authors.forename: Shujing
authors.initials: S
authors.lastname: Li
authors.affiliation: School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Wang
authors.affiliation: School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024, China.
authors.forename: Zhaojun
authors.initials: Z
authors.lastname: Jia
authors.affiliation: School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024, China.
authors.forename: Alan K
authors.initials: AK
authors.lastname: Chang
authors.affiliation: School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024, China.
authors.forename: Pengsha
authors.initials: P
authors.lastname: Pang
authors.affiliation: School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024, ChinaSchool of Life Science and Medicine, Dalian University of Technology, Panjin 124221, China wuhj@dlut.edu.cn.
authors.forename: Huijian
authors.initials: H
authors.lastname: Wu
mesh_terms: D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics*; D006801:Humans; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D061986:MCF-7 Cells; D010766:Phosphorylation; D015398:Signal Transduction; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics / Q000378:metabolism*; D058207:Sumoylation; D014158:Transcription, Genetic
chemical_list: C103316:GPS2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D025841:Small Ubiquitin-Related Modifier Proteins