title: SUMOylation regulates nuclear localization and stability of TRAIP/RNF206.
abstract: TRAIP/RNF206 plays diverse roles in cell cycle progression, DNA damage response, and DNA repair pathways. Physiological importance of TRAIP is highlighted by the identification of pathogenic mutations of TRAIP gene in patients diagnosed with primordial dwarfism. Although the diverse functions of TRAIP in the nucleus have been well characterized, molecular mechanism of TRAIP retention in the nucleus has not been determined. Here, we discovered that TRAIP is post-translationally modified by the small ubiquitin-like protein (SUMO). In addition, we identified five SUMOylation sites in TRAIP, and successfully generated SUMOylation deficient mutant of TRAIP. In an attempt to define the functional roles of TRAIP SUMOylation, we discovered that SUMOylation deficient TRAIP is not retained in the nucleus. In addition, protein stability of SUMOylation deficient TRAIP is lower than wild type TRAIP, demonstrating that SUMOylation is critical for both proper subcellular localization and protein stability of TRAIP. Taken together, these findings improve the understanding clinical implication of TRAIP in various diseases including primordial dwarfism and cancers.
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University (SKKU), Suwon 440-746, South Korea.
authors.forename: I Seul
authors.initials: IS
authors.lastname: Park
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University (SKKU), Suwon 440-746, South Korea.
authors.forename: Ye gi
authors.initials: Yg
authors.lastname: Han
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University (SKKU), Suwon 440-746, South Korea.
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Chung
authors.affiliation: College of Pharmacy, Korea University, Sejong City 339-700, South Korea.
authors.forename: Yong Woo
authors.initials: YW
authors.lastname: Jung
authors.affiliation: Department of Biological Sciences, Sookmyung Women's University, Seoul 04310, South Korea. Electronic address: yhkim@sookmyung.ac.kr.
authors.forename: Yonghwan
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University (SKKU), Suwon 440-746, South Korea. Electronic address: khtcat@skku.edu.
authors.forename: Hongtae
authors.initials: H
authors.lastname: Kim
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D055550:Protein Stability; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D058207:Sumoylation / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D025841:Small Ubiquitin-Related Modifier Proteins; C000607340:TRAIP protein, human; D044767:Ubiquitin-Protein Ligases
keywords: Protein degradation; SUMOylation; Subcellular localization; TRAIP