title: O-Fucosylation of CCN1 is required for its secretion.
abstract: The matricellular protein CCN1, also known as Cyr61, is a secreted ligand and has numerous functions. Human CCN1 contains one predicted O-fucosylation site in the thrombospondin type-1 repeat (TSR1) domain at Thr(242). In this report, we demonstrated that CCN1 is O-fucosylated at Thr(242) using mass spectrometry. Deficiency of O-fucosylation resulted in the decrement of the cell surface localization and the secretion of CCN1. Furthermore, knockdown of protein O-fucosyltransferase 2, which modifies a specific Ser/Thr residue in the TSR1 domain, decreased secreted levels of CCN1. These results demonstrated that O-fucosylation of CCN1 at Thr(242) regulates its secretion.
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Niwa
authors.affiliation: Biomolecular Characterization Unit, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako 351-0198, Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Biomolecular Characterization Unit, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako 351-0198, Japan.
authors.forename: Naoshi
authors.initials: N
authors.lastname: Dohmae
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan. Electronic address: simizu@applc.keio.ac.jp.
authors.forename: Siro
authors.initials: S
authors.lastname: Simizu
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor; D055515:Cysteine-Rich Protein 61 / Q000737:chemistry* / Q000378:metabolism*; D005643:Fucose / Q000378:metabolism*; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D013058:Mass Spectrometry; D009154:Mutation; D013912:Threonine / Q000737:chemistry*
chemical_list: C501848:CCN1 protein, human; D055515:Cysteine-Rich Protein 61; D005643:Fucose; D013912:Threonine; D005647:Fucosyltransferases; C495567:POFUT2 protein, human
keywords: CCN1; Glycosylation; Mass spectrometry; O-fucosylation; Protein O-fucosyltransferase2 (Pofut2)