O-Fucosylation of CCN1 is required for its secretion

FEBS Lett. 2015 Oct 24;589(21):3287-93. doi: 10.1016/j.febslet.2015.09.012. Epub 2015 Sep 28.

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.

Keywords: CCN1; Glycosylation; Mass spectrometry; O-fucosylation; Protein O-fucosyltransferase2 (Pofut2).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cell Line, Tumor
  • Cysteine-Rich Protein 61 / chemistry*
  • Cysteine-Rich Protein 61 / metabolism*
  • Fucose / metabolism*
  • Fucosyltransferases / genetics
  • Fucosyltransferases / metabolism
  • Glycosylation
  • Humans
  • Mass Spectrometry
  • Mutation
  • Threonine / chemistry*

Substances

  • CCN1 protein, human
  • Cysteine-Rich Protein 61
  • Fucose
  • Threonine
  • Fucosyltransferases
  • POFUT2 protein, human