CRL1-FBXO11 Promotes Cdt2 Ubiquitylation and Degradation and Regulates Pr-Set7/Set8-Mediated Cellular Migration

被引：79

作者：

Abbas, Tarek ^{[1
,2
]}

Mueller, Adam C. ^{[1
]}

Shibata, Etsuko ^{[1
]}

Keaton, Mignon ^{[1
]}

Rossi, Mario ^{[3
]}

Dutta, Anindya ^{[1
]}

机构：

[1] Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA

[2] Univ Virginia, Sch Med, Dept Radiat Oncol, Charlottesville, VA 22908 USA

[3] Max Planck Gesell, CONICET, Inst Invest Biomed Buenos Aires IbioBA, RA-2390 Buenos Aires, DF, Argentina

来源：

MOLECULAR CELL | 2013年 / 49卷 / 06期

关键词：

EPITHELIAL-MESENCHYMAL TRANSITION; MATRIX-ASSOCIATED PROTEIN; E3 UBIQUITIN LIGASES; S-PHASE; HISTONE METHYLTRANSFERASE; CYCLE PROGRESSION; MAMMALIAN-CELLS; CANCER-CELLS; DNA-DAMAGE; NUCLEAR;

D O I：

10.1016/j.molcel.2013.02.003

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

The Cul4-Cdt2 (CRL4(Cdt2)) E3 ubiquitin ligase is a master regulator of cell-cycle progression and genome stability. Despite its central role in the degradation of many cell-cycle regulators, e.g., Cdt1, p21, and Pr-Set7/Set8, little is known about the regulation of its activity. We report that Cdt2 is autoubiquitylated by the CRL4A E3 ubiquitin ligase. Cdt2 is additionally polyubiquitylated and degraded by Cul1-FBXO11 (CRL1(FBXO11)). CRL1(FBXO11)-mediated degradation of Cdt2 stabilizes p21 and Set8, and this is important during the response to TGF-beta, with the Set8 induction being important for turning off the activation of Smad2. The migration of epithelial cells is also stimulated by CRL1(FBXO11)-mediated downregulation of Cdt2 and the consequent stabilization of Set8. This is an interesting example of cross-regulation between specific Cullin 4 and Cullin 1 E3 ubiquitin ligases and highlights the role of ubiquitylation in regulating cellular responses to TGF-beta and the migration of epithelial cells.

引用

页码：1147 / 1158

页数：12

共 41 条

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