title: Wwp2 targets SRG3, a scaffold protein of the SWI/SNF-like BAF complex, for ubiquitination and degradation.
abstract: SRG3 plays essential roles both in early mouse embryogenesis and in extra-embryonic vascular development. As one of the core components of the SWI/SNF-like BAF complex, SRG3 serves as the scaffold protein and its protein level controls the stability of the BAF complex, which controls diverse physiological processes through transcriptional regulation. However, little is known about how the protein level of SRG3 is regulated in mammalian cells. Previously, we identified a murine ubiquitin ligase (Wwp2) and demonstrated that it interacts with pluripotency-associated key transcription factor Oct4 and RNA polymerase II large subunit Rpb1, promoting their ubiquitination and degradation. Here, we report that Wwp2 acts as a ubiquitin ligase of SRG3. Our results show that Wwp2 and SRG3 form protein complexes and co-localize in the nucleus in mammalian cells. The interaction is mediated through the WW domain of Wwp2 and the PPPY motif of SRG3, respectively. Importantly, Wwp2 promotes ubiquitination and degradation of SRG3 through the ubiquitin-proteasome system. The expression of a catalytically inactive mutant of Wwp2 abolishes SRG3 ubiquitination. Collectively, our study opens up a new avenue to understand how the protein level of SRG3 is regulated in mammalian cells.
authors.affiliation: Shanghai Stem Cell Institute, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Xinlong
authors.initials: X
authors.lastname: Luo
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Beibei
authors.initials: B
authors.lastname: Wang
authors.affiliation: Shanghai Stem Cell Institute, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Tang
authors.affiliation: Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Junmei
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Yingming
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Shanghai Stem Cell Institute, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: biolihui@163.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Shanghai Stem Cell Institute, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: yjin@sibs.ac.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jin
mesh_terms: D000818:Animals; D002868:Chromosomal Proteins, Non-Histone; D057809:HEK293 Cells; D006801:Humans; D008322:Mammals / Q000378:metabolism; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism*; D011485:Protein Binding; D059748:Proteolysis; D014157:Transcription Factors / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D046912:Multiprotein Complexes; C101681:SMARCC1 protein, human; C491090:Smarcc1 protein, mouse; D014157:Transcription Factors; C465283:WWP2 protein, human; C487995:Wwp2 protein, mouse; D044767:Ubiquitin-Protein Ligases
keywords: Protein stability; SRG3; SWI/SNF-like BAF complex; Ubiquitination; Wwp2