title: O-GlcNAc transferase catalyzes site-specific proteolysis of HCF-1.
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.
authors.affiliation: Center for Integrative Genomics, University of Lausanne, Switzerland.
authors.forename: Francesca
authors.initials: F
authors.lastname: Capotosti
authors.forename: Sophie
authors.initials: S
authors.lastname: Guernier
authors.forename: Fabienne
authors.initials: F
authors.lastname: Lammers
authors.forename: Patrice
authors.initials: P
authors.lastname: Waridel
authors.forename: Yong
authors.initials: Y
authors.lastname: Cai
authors.forename: Jingji
authors.initials: J
authors.lastname: Jin
authors.forename: Joan W
authors.initials: JW
authors.lastname: Conaway
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Conaway
authors.forename: Winship
authors.initials: W
authors.lastname: Herr
mesh_terms: D000595:Amino Acid Sequence; D002453:Cell Cycle; D006031:Glycosylation; D051863:Host Cell Factor C1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D021122:Protein Subunits / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: C497692:HCFC1 protein, human; D051863:Host Cell Factor C1; D021122:Protein Subunits; D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase