The SCF-Fbw7 ubiquitin ligase degrades MED13 and MED13L and regulates CDK8 module association with Mediator

被引：96

作者：

Davis, Michael A. ^{[1
,2
]}

Larimore, Elizabeth A. ^{[1
,2
]}

Fissel, Brian M. ^{[1
,2
]}

Swanger, Jherek ^{[1
,2
]}

Taatjes, Dylan J. ^{[3
]}

Clurman, Bruce E. ^{[1
,2
]}

机构：

[1] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98117 USA

[2] Fred Hutchinson Canc Res Ctr, Human Biol Div, Seattle, WA 98117 USA

[3] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80303 USA

来源：

GENES & DEVELOPMENT | 2013年 / 27卷 / 02期

关键词：

Fbw7; MED13/13L; CDK8; SCF; Mediator; TUMOR-SUPPRESSOR; CYCLIN-E; MULTISITE PHOSPHORYLATION; COMPLEX; UBIQUITYLATION; INACTIVATION; RECOGNITION; FBXW7/HCDC4; CANCER; HCDC4;

D O I：

10.1101/gad.207720.112

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The Mediator complex is an essential transcription regulator that bridges transcription factors with RNA polymerase II. This interaction is controlled by dynamic interactions between Mediator and the CDK8 module, but the mechanisms governing CDK8 module-Mediator association remain poorly understood. We show that Fbw7, a tumor suppressor and ubiquitin ligase, binds to CDK8-Mediator and targets MED13/13L for degradation. MED13/13L physically link the CDK8 module to Mediator, and Fbw7 loss increases CDK8 module-Mediator association. Our work reveals a novel mechanism regulating CDK8 module-Mediator association and suggests an expanded role for Fbw7 in transcriptional control and an unanticipated relationship with the CDK8 oncogene.

引用

页码：151 / 156

页数：6

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