Cell. 2011 Feb 4;144(3):376-88.
O-GlcNAc Transferase Catalyzes Site-Specific Proteolysis of HCF-1.
Center for Integrative Genomics, University of Lausanne, Génopode, 1015 Lausanne, Switzerland.
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]
- 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