O-GlcNAc transferase catalyzes site-specific proteolysis of HCF-1

Cell. 2011 Feb 4;144(3):376-88. doi: 10.1016/j.cell.2010.12.030.

Abstract

The human epigenetic cell-cycle regulator HCF-1 undergoes an unusual proteolytic maturation process resulting in stably associated HCF-1(N) and HCF-1(C) subunits that regulate different aspects of the cell cycle. Proteolysis occurs at six centrally located HCF-1(PRO)-repeat sequences and is important for activation of HCF-1(C)-subunit functions in M phase progression. We show here that the HCF-1(PRO) repeat is recognized by O-linked β-N-acetylglucosamine transferase (OGT), which both O-GlcNAcylates the HCF-1(N) subunit and directly cleaves the HCF-1(PRO) repeat. Replacement of the HCF-1(PRO) repeats by a heterologous proteolytic cleavage signal promotes HCF-1 proteolysis but fails to activate HCF-1(C)-subunit M phase functions. These results reveal an unexpected role of OGT in HCF-1 proteolytic maturation and an unforeseen nexus between OGT-directed O-GlcNAcylation and proteolytic maturation in HCF-1 cell-cycle regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Cycle
  • Glycosylation
  • Host Cell Factor C1 / chemistry
  • Host Cell Factor C1 / genetics
  • Host Cell Factor C1 / metabolism*
  • Humans
  • Molecular Sequence Data
  • Mutation
  • N-Acetylglucosaminyltransferases / metabolism*
  • Protein Processing, Post-Translational*
  • Protein Subunits / metabolism
  • Sequence Alignment

Substances

  • HCFC1 protein, human
  • Host Cell Factor C1
  • Protein Subunits
  • N-Acetylglucosaminyltransferases
  • O-GlcNAc transferase