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Ras induces mediator complex exchange on C/EBP beta.

Xianming Mo·Elisabeth Kowenz-Leutz·Hong Xu·Achim Leutz
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Abstract

C/EBPbeta is an intrinsically repressed transcription factor that regulates genes involved in differentiation, proliferation, tumorigenesis, and apoptosis. C/EBPbeta acts as a repressor that is turned into an activator by the Ras oncoprotein through phosphorylation of a MAPK site. C/EBPbeta activation is accompanied by a conformational change. Active and repressive C/EBPbeta 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/EBPbeta. Oncogenic Ras signaling or activating mutations in C/EBPbeta selects the transcriptionally active Mediator complex that also associates with RNA polymerase II. These results show that a Ras-induced structural alteration of C/EBPbeta determines differential gene activation through selective interaction with distinct Mediator complexes.

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ApoptosisCCAAT-Enhancer-Binding Protein-betaChromatinCyclin-Dependent Kinase 8Cyclin-Dependent KinasesEnzyme ActivationGenes, ReporterGlutathione TransferaseHeLa CellsHumansMAP Kinase Signaling SystemModels, GeneticMutationPrecipitin TestsProtein BindingProtein ConformationProtein Structure, TertiaryRNARNA Polymerase IIRecombinant Fusion ProteinsSignal TransductionTrans-ActivatorsTranscription, GeneticTranscriptional Activationras ProteinsJournal ArticleResearch Support, Non-U.S. Gov't

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Xianming Mo, Elisabeth Kowenz-Leutz, Hong Xu, Achim Leutz. 2004-01-30. Ras induces mediator complex exchange on C/EBP beta.. https://doi.org/10.1016/s1097-2765(03)00521-5

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