title: PIAS1-mediated sumoylation promotes STUbL-dependent proteasomal degradation of the human telomeric protein TRF2.
abstract: The human telomeric protein TRF2 protects chromosome ends by facilitating their organization into the protective capping structure. Here we show that the stability of TRF2 is regulated via modification by the small ubiquitin-like modifiers (SUMO). TRF2 specifically interacts with and is sumoylated by PIAS1 in mammalian cells. The proteasome inhibitor stabilizes SUMO-conjugated TRF2 without affecting the level of unmodified TRF2, suggesting that SUMO conjugation is required for proteasomal degradation of TRF2. We also show that RNF4, a mammalian SUMO-targeted ubiquitin ligase, interacts with TRF2 in a SUMO-dependent manner and preferentially targets SUMO-conjugated TRF2 for ubiquitination. Collectively, our data demonstrate that the PIAS1-mediated sumoylation status of TRF2 serves as a molecular switch that controls the level of TRF2 at telomeres.
authors.affiliation: Department of Integrated Omics for Biomedical Science, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Joonyoung
authors.initials: J
authors.lastname: Her
authors.affiliation: Department of Integrated Omics for Biomedical Science, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Yu Young
authors.initials: YY
authors.lastname: Jeong
authors.affiliation: Department of Integrated Omics for Biomedical Science, Yonsei University, Seoul 120-749, Republic of Korea; Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea. Electronic address: topoviro@yonsei.ac.kr.
authors.forename: In Kwon
authors.initials: IK
authors.lastname: Chung
mesh_terms: D002460:Cell Line; D057809:HEK293 Cells; D006801:Humans; D061986:MCF-7 Cells; D009687:Nuclear Proteins / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors / Q000494:pharmacology; D050828:Protein Inhibitors of Activated STAT / Q000378:metabolism*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D058207:Sumoylation; D016615:Telomere / Q000378:metabolism; D035341:Telomeric Repeat Binding Protein 2 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D009687:Nuclear Proteins; C106529:PIAS1 protein, human; D061988:Proteasome Inhibitors; D050828:Protein Inhibitors of Activated STAT; C114070:RNF4 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; C504753:TERF2 protein, human; D035341:Telomeric Repeat Binding Protein 2; D014157:Transcription Factors; D046988:Proteasome Endopeptidase Complex
keywords: Protein inhibitor of activated STAT; Ring-finger protein 4; Sumoylation; Telomere; Telomeric repeat binding factor 2; Ubiquitination