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.