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O-GlcNAc transferase catalyzes site-specific proteolysis of HCF-1 |
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| Authors: | Capotosti Francesca Guernier Sophie Lammers Fabienne Waridel Patrice Cai Yong Jin Jingji Conaway Joan W Conaway Ronald C Herr Winship |
| Affiliation: | 1 Center for Integrative Genomics, University of Lausanne, Génopode, 1015 Lausanne, Switzerland 2 Protein Analysis Facility, Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland 3 Stowers Institute for Medical Research, Kansas City, MO 64110, USA 4 Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA |
| 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. |
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