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

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...

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Veröffentlicht in:Cell 2011-02, Vol.144 (3), p.376-388
Hauptverfasser: Capotosti, Francesca, Guernier, Sophie, Lammers, Fabienne, Waridel, Patrice, Cai, Yong, Jin, Jingji, Conaway, Joan W., Conaway, Ronald C., Herr, Winship
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Sprache:eng
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Zusammenfassung: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-1PRO 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. [Display omitted] [Display omitted] ► 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
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2010.12.030