Ras induces mediator complex exchange on C/EBPβ

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.