title: The SCF-Fbw7 ubiquitin ligase degrades MED13 and MED13L and regulates CDK8 module association with Mediator.
abstract: 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.
authors: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98117, USA.
authors: Michael A
authors: MA
authors: Davis
authors: Elizabeth A
authors: EA
authors: Larimore
authors: Brian M
authors: BM
authors: Fissel
authors: Jherek
authors: J
authors: Swanger
authors: Dylan J
authors: DJ
authors: Taatjes
authors: Bruce E
authors: BE
authors: Clurman
mesh_terms: D045744:Cell Line, Tumor; D056850:Cyclin-Dependent Kinase 8 / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D056892:Mediator Complex / Q000378:metabolism*; D011485:Protein Binding; D059748:Proteolysis; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: C488666:MED13 protein, human; C480067:MED13L protein, human; D056892:Mediator Complex; D044843:SKP Cullin F-Box Protein Ligases; D056850:Cyclin-Dependent Kinase 8