title: SUMO Modification Reverses Inhibitory Effects of Smad Nuclear Interacting Protein-1 in TGF-β Responses.
abstract: SNIP1 (Smad nuclear interacting protein 1) is a transcription repressor for the TGF-β and NF-κB signaling pathways through disrupting the recruitment of co-activator p300. However, it is unclear how the functions of SNIP1 in the TGF-β signaling pathway are controlled. Our present studies show that SNIP1 is covalently modified by small ubiquitin-like modifier (SUMO) in vitro and in vivo at three lysine sites: Lys5, Lys30, and Lys108, with Lys30being the major SUMO modification site. SUMOylation of SNIP1 is enhanced by SUMO E3 ligase PIAS proteins and inhibited by SUMO proteases SENP1/2. Furthermore, we find that SUMOylation of SNIP1 attenuates its inhibitory effect in TGF-β signaling because the SUMO-conjugated form of SNIP1 exhibits impaired ability to disrupt the formation of Smad complex and the interaction between p300 and Smads. Subsequently, SUMOylation of SNIP1 leads to the loss of SNIP1-mediated inhibition on expression of the TGF-β target genes PAI-1 and MMP2 and eventually enhances TGF-β-regulated cell migration and invasion.
authors.affiliation: From the Life Sciences Institute, Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China,; the Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, and; the Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: Sisi
authors.initials: S
authors.lastname: Liu
authors.affiliation: the Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, and.
authors.forename: Jianyin
authors.initials: J
authors.lastname: Long
authors.affiliation: From the Life Sciences Institute, Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yuan
authors.affiliation: From the Life Sciences Institute, Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Mingjie
authors.initials: M
authors.lastname: Zheng
authors.affiliation: From the Life Sciences Institute, Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Mu
authors.initials: M
authors.lastname: Xiao
authors.affiliation: the Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: Jianming
authors.initials: J
authors.lastname: Xu
authors.affiliation: the Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, and.
authors.forename: Xia
authors.initials: X
authors.lastname: Lin
authors.affiliation: From the Life Sciences Institute, Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China,; the Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, and; the Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, Texas 77030. Electronic address: fenglab@zju.edu.cn.
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Feng
mesh_terms: D000072283:A549 Cells; D000818:Animals; D019556:COS Cells; D002465:Cell Movement / Q000502:physiology*; D002522:Chlorocebus aethiops; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000235:genetics; D050828:Protein Inhibitors of Activated STAT / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins; D025842:SUMO-1 Protein / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D058207:Sumoylation / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D017395:Plasminogen Activator Inhibitor 1; D050828:Protein Inhibitors of Activated STAT; D016601:RNA-Binding Proteins; C051321:SERPINE1 protein, human; C411545:SNIP1 protein, human; D025842:SUMO-1 Protein; D016212:Transforming Growth Factor beta; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: SMAD transcription factor; SNIP1; signaling; sumoylation; transcription; transforming growth factor beta (TGF-β)