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.
Mesh Terms:
Apoptosis, CCAAT-Enhancer-Binding Protein-beta, Chromatin, Cyclin-Dependent Kinase 8, Cyclin-Dependent Kinases, Enzyme Activation, Genes, Reporter, Glutathione Transferase, Hela Cells, Humans, MAP Kinase Signaling System, Models, Genetic, Mutation, Precipitin Tests, Protein Binding, Protein Conformation, Protein Structure, Tertiary, RNA, RNA Polymerase II, Recombinant Fusion Proteins, Signal Transduction, Trans-Activators, Transcription, Genetic, Transcriptional Activation, ras Proteins
Mol. Cell
Date: Jan. 30, 2004
Download Curated Data For This Publication
7736
Switch View:
  • Interactions 5