CRL1-FBXO11 promotes Cdt2 ubiquitylation and degradation and regulates Pr-Set7/Set8-mediated cellular migration.
CRL1-FBXO11 promotes Cdt2 ubiquitylation and degradation and regulates Pr-Set7/Set8-mediated cellular migration.
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DOI：
10.1016/j.molcel.2013.02.003
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发表时间：
2013-03-28
期刊：
影响因子：
16
通讯作者：
Dutta, Anindya
中科院分区：
文献类型：
--
作者：
Abbas, Tarek;Mueller, Adam C.;Shibata, Etsuko;Keaton, Mignon;Rossi, Mario;Dutta, Anindya
Cul 4-Cdt 2（CRL 4Cdt 2）E3泛素连接酶是细胞周期进程和基因组稳定性的主要调节剂。尽管它在许多细胞周期调节因子（如Cdt 1、p21和Pr-Set 7/Set 8）的降解中起着重要作用，但对其活性的调节知之甚少。我们报告，Cdt 2是autoubiquitylated的CRL 4A E3泛素连接酶。Cdt 2还被Cul 1-FBXO 11（CRL 1FBXO 11）多聚泛素化和降解。CRL 1FBXO 11介导的Cdt 2降解稳定了p21和Set 8，这在对TGF-β的反应过程中很重要，Set 8诱导对于关闭Smad 2的激活很重要。上皮细胞的迁移也受到CRL 1FBXO 11介导的Cdt 2下调和随后Set 8稳定的刺激。这是特异性cullin 4和cullin 1 E3泛素连接酶之间交叉调节的新实例，并突出了泛素化在调节细胞对TGF-β的反应和上皮细胞迁移中的作用。
The Cul4-Cdt2 (CRL4Cdt2) 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 (CRL1FBXO11). CRL1FBXO11-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 CRL1FBXO11-mediated downregulation of Cdt2 and the consequent stabilization of Set8. This is a novel 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.
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影响因子：
16
作者：
Oda H;Hübner MR;Beck DB;Vermeulen M;Hurwitz J;Spector DL;Reinberg D
通讯作者：
Reinberg D
影响因子：
16
作者：
Abbas T;Shibata E;Park J;Jha S;Karnani N;Dutta A
通讯作者：
Dutta A
影响因子：
21.3
作者：
Angers, S;Thorpe, CJ;Moon, RT
通讯作者：
Moon, RT
影响因子：
8
作者：
Mackintosh, C.;Ordonez, J. L.;de Alava, E.
通讯作者：
de Alava, E.
影响因子：
2.7
作者：
Kopanja D;Roy N;Stoyanova T;Hess RA;Bagchi S;Raychaudhuri P
通讯作者：
Raychaudhuri P