Ras induces mediator complex exchange on C/EBP beta.
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.
Mo
Xianming
X
Max-Delbrück-Center for Molecular Medicine, Robert-Roessle-Str. 10, 13092 Berlin, Germany.
Kowenz-Leutz
Elisabeth
E
Xu
Hong
H
Leutz
Achim
A
D017209:Apoptosis; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D056850:Cyclin-Dependent Kinase 8; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004789:Enzyme Activation; D017930:Genes, Reporter; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D008957:Models, Genetic; D009154:Mutation; D011233:Precipitin Tests; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D018631:ras Proteins / Q000502:physiology*
D022782:CCAAT-Enhancer-Binding Protein-beta; C117286:CRSP protein, human; D002843:Chromatin; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D012313:RNA; D005982:Glutathione Transferase; C095686:CDK8 protein, human; D056850:Cyclin-Dependent Kinase 8; D018844:Cyclin-Dependent Kinases; D012319:RNA Polymerase II; D018631:ras Proteins