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

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....

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Published inGenes & development Vol. 27; no. 2; pp. 151 - 156
Main Authors Davis, Michael A, Larimore, Elizabeth A, Fissel, Brian M, Swanger, Jherek, Taatjes, Dylan J, Clurman, Bruce E
Format Journal Article
LanguageEnglish
Published United States Cold Spring Harbor Laboratory Press 15.01.2013
Subjects
Cell Line, Tumor
Cyclin-Dependent Kinase 8 - metabolism
Gene Expression Regulation, Neoplastic
HEK293 Cells
HeLa Cells
Humans
Mediator Complex - metabolism
Protein Binding
Proteolysis
Research Communication
SKP Cullin F-Box Protein Ligases - genetics
SKP Cullin F-Box Protein Ligases - metabolism
Ubiquitination
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Summary: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.
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ISSN:0890-9369
1549-5477
DOI:10.1101/gad.207720.112