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Ras induces mediator complex exchange on C/EBPβ

Item Type:Article
Title:Ras induces mediator complex exchange on C/EBPβ
Creators Name:Mo, X.M. and Kowenz-Leutz, E. and Xu, H. and Leutz, A.
Abstract:C/EBP{beta} is an intrinsically repressed transcription factor that regulates genes involved in differentiation, proliferation, tumorigenesis, and apoptosis. C/EBPβ acts as a repressor that is turned into an activator by the Ras oncoprotein through phosphorylation of a MAPK site. C/EBP{beta} activation is accompanied by a conformational change. Active and repressive C/EBP{beta} interacts with multisubunit Mediator complexes through the CRSP130/Sur2 subunit. The CRSP130/Sur2 subunit is common to two distinct types of Mediator complexes, characterized by CRSP70 and CDK8 proteins as transcriptionally active and inactive Mediator, respectively. Knockdown of CRSP130/Sur2 prevents Mediator binding and transactivation through C/EBP{beta}. Oncogenic Ras signaling or activating mutations in C/EBP{beta} selects the transcriptionally active Mediator complex that also associates with RNA polymerase II. These results show that a Ras-induced structural alteration of C/EBP{beta} determines differential gene activation through selective interaction with distinct Mediator complexes.
Keywords:Apoptosis, CCAAT-Enhancer-Binding Protein-Beta, Chromatin, Cyclin-Dependent Kinases, Enzyme Activation, Genetic Models, Genetic Transcription, Glutathione Transferase, Hela Cells, MAP Kinase Signaling System, Mutation, Precipitin Tests, Protein Binding, Protein Conformation, Ras Proteins, Recombinant Fusion Proteins, Reporter Genes, RNA, RNA Polymerase II, Signal Transduction, Trans-Activation, Trans-Activators, Tertiaryv Protein Structure
Source:Molecular Cell
Publisher:Cell Press
Page Range:241-250
Date:30 January 2004
Official Publication:https://doi.org/10.1016/S1097-2765(03)00521-5
PubMed:View item in PubMed

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