Ras Induces Mediator Complex Exchange on C/EBP Beta

Mol Cell. 2004 Jan 30;13(2):241-50. doi: 10.1016/s1097-2765(03)00521-5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • CCAAT-Enhancer-Binding Protein-beta / metabolism*
  • Chromatin / metabolism
  • Cyclin-Dependent Kinase 8
  • Cyclin-Dependent Kinases / metabolism
  • Enzyme Activation
  • Genes, Reporter
  • Glutathione Transferase / metabolism
  • HeLa Cells
  • Humans
  • MAP Kinase Signaling System
  • Models, Genetic
  • Mutation
  • Precipitin Tests
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Tertiary
  • RNA / metabolism
  • RNA Polymerase II / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction
  • Trans-Activators / metabolism
  • Transcription, Genetic
  • Transcriptional Activation
  • ras Proteins / physiology*

Substances

  • CCAAT-Enhancer-Binding Protein-beta
  • CRSP protein, human
  • Chromatin
  • Recombinant Fusion Proteins
  • Trans-Activators
  • RNA
  • Glutathione Transferase
  • CDK8 protein, human
  • Cyclin-Dependent Kinase 8
  • Cyclin-Dependent Kinases
  • RNA Polymerase II
  • ras Proteins