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

被引：187

作者：

Capotosti, Francesca

Guernier, Sophie

Lammers, Fabienne

Waridel, Patrice ^{[1
]}

Cai, Yong ^{[2
]}

Jin, Jingji ^{[2
]}

Conaway, Joan W. ^{[2
,3
]}

Conaway, Ronald C. ^{[2
,3
]}

Herr, Winship ^{[1
]}

机构：

[1] Univ Lausanne, Ctr Integrat Genom, Fac Biol & Med, Prot Anal Facil, CH-1015 Lausanne, Switzerland

[2] Stowers Inst Med Res, Kansas City, MO 64110 USA

[3] Univ Kansas, Med Ctr, Dept Biochem & Mol Biol, Kansas City, KS 66160 USA

来源：

CELL | 2011年 / 144卷 / 03期

基金：

瑞士国家科学基金会;

关键词：

N-ACETYLGLUCOSAMINE; COACTIVATOR HCF-1; TERMINAL SUBUNIT; PROTEINS; NUCLEAR; GLYCOSYLATION; COMPLEX; FAMILY; DOMAIN; VP16;

D O I：

10.1016/j.cell.2010.12.030

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 beta-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.

引用

页码：376 / 388

页数：13

共 47 条

[1] O-linked β-N-acetylglucosamine (O-GlcNAc): Extensive crosstalk with phosphorylation to regulate signaling and transcription in response to nutrients and stress [J].