title: A role for Mediator complex subunit MED13L in Rb/E2F-induced growth arrest.
abstract: The Rb/E2F pathway is deregulated in virtually all human tumors. It is clear that, in addition to Rb itself, essential cofactors required for transcriptional repression and silencing of E2F target genes are mutated or lost in cancer. To identify novel cofactors required for Rb/E2F-mediated inhibition of cell proliferation, we performed a genome-wide short hairpin RNA screen. In addition to several known Rb cofactors, the screen identified components of the Mediator complex, a large multiprotein coactivator required for RNA polymerase II transcription. We show that the Mediator complex subunit MED13L is required for Rb/E2F control of cell growth, the complete repression of cell cycle target genes, and cell cycle inhibition.
authors.affiliation: Duke Institute for Genome Sciences & Policy, Duke University Medical Center, Durham, NC, USA.
authors.forename: S P
authors.initials: SP
authors.lastname: Angus
authors.forename: J R
authors.initials: JR
authors.lastname: Nevins
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints / Q000235:genetics; D002460:Cell Line; D016922:Cellular Senescence / Q000235:genetics; D050684:E2F Transcription Factors / Q000235:genetics / Q000378:metabolism*; D050700:E2F5 Transcription Factor / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D056892:Mediator Complex / Q000378:metabolism*; D051379:Mice; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods; D034741:RNA, Small Interfering / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D050684:E2F Transcription Factors; D050700:E2F5 Transcription Factor; C480067:MED13L protein, human; D056892:Mediator Complex; D034741:RNA, Small Interfering; D016160:Retinoblastoma Protein