@article{fc450990422040609f0fe64bdf5ac71f,
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-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:",
author = "Francesca Capotosti and Sophie Guernier and Fabienne Lammers and Patrice Waridel and Yong Cai and Jingji Jin and Conaway, {Joan W.} and Conaway, {Ronald C.} and Winship Herr",
note = "Funding Information: We thank T.M. Kristie and J.A. Hanover for the HCF-1nc and the bacterial OGT expression vectors, respectively; M. Boutros and A. Wilson for the HCF-1 ΔPROrep2 construct; R.S. Haltiwanger for the α-OGT antibody; E. Julien and D.J. Aufiero for the N13 and C18 antibodies; S.S. Taylor for the Flp-In-HeLa cells; M. Quadroni for advice with the mass spectrometry analysis; L. Capponi, P. L'H{\^o}te, and M. McLaird for technical support; and J.H. Reina for art design. We thank N. Hernandez, J. Michaud, and S.H. Verhelst for critical reading of the manuscript; and V. Zoete, O. Michielin, N. Hernandez, J. M{\"u}ller, P. Schneider, and K. Struhl for discussion. This study was supported by the Stowers Institute for Medical Research and the Helen Nelson Medical Research Fund at the Greater Kansas City Community Foundation to J.W.C. and R.C.C. and by the Swiss National Science Foundation, Oncosuisse, and the University of Lausanne to W.H. ",
year = "2011",
month = feb,
day = "4",
doi = "10.1016/j.cell.2010.12.030",
language = "English (US)",
volume = "144",
pages = "376--388",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "3",
}