O‐fucosylation of CCN1 is required for its secretion. Issue 21 (28th September 2015)

• Record Type: Journal Article
• Authors: Niwa, Yuki; Suzuki, Takehiro; Dohmae, Naoshi; Simizu, Siro
• Is Part Of: FEBS letters. Volume 589:Issue 21(2015)
• Page Start: 3287
• Page End: 3293
• Publication Date: 2015-09-28
• Subjects: IGFBP -- insulin-like growth factor-binding protein -- vWC -- von Willebrand factor type C repeat -- TSR1 -- thrombospondin type-1 repeat -- CT -- cysteine knot motif -- HSPG -- heparan sulfate proteoglycan -- EGF -- epidermal growth factor -- ER -- endoplasmic reticulum -- Pofut -- proteinO-fucosyltransferase -- CM -- conditioned medium -- DMEM -- Dulbecco's modified Eagle's medium -- CBB -- Coomassie Brilliant Blue -- PBS -- phosphate-buffered saline -- CCN1 -- Glycosylation -- Mass spectrometry -- O-fucosylation -- ProteinO-fucosyltransferase2 (Pofut2); Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2015.09.012
• Languages: English
• ISSNs: 0014-5793

Abstract

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. Abstract : Human CCN1 is O ‐fucosylated at Thr 242 . O ‐fucosylation‐defective mutant of CCN1 decreased the secretion level. Pofut2‐mediated O ‐fucosylation is required for the secretion of CCN1. Secretion of CCN1 is regulated by O ‐fucosylation.