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

Francesca Capotosti, Sophie Guernier, Fabienne Lammers, Patrice Waridel, Yong Cai, Jingji Jin, Joan W. Conaway, Ronald C. Conaway, Winship Herr

Research output: Contribution to journalArticlepeer-review

170 Scopus citations

Abstract

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

Original languageEnglish (US)
Pages (from-to)376-388
Number of pages13
JournalCell
Volume144
Issue number3
DOIs
StatePublished - Feb 4 2011
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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