Cell; group Herr

Cell. 2011 Feb 4;144(3):376-88.

O-GlcNAc Transferase Catalyzes Site-Specific Proteolysis of HCF-1.

Capotosti F, Guernier S, Lammers F, Waridel P, Cai Y, Jin J, Conaway JW, Conaway RC, Herr W.

Center for Integrative Genomics, University of Lausanne, Génopode, 1015 Lausanne, Switzerland.

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. PAPERCLIP:

Copyright © 2011 Elsevier Inc. All rights reserved.

PMID: 21295698 [PubMed - in process]

Highlights

  • OGT is a protease responsible for human HCF-1 proteolytic maturation
  • OGT recognizes and cleaves an extended 21 amino acid sequence
  • HCF-1 proteolytic maturation involves HCF-1 O-GlcNAcylation
  • HCF-1PRO-repeat-induced proteolysis activates HCF-1 M phase cell-cycle functions