Oncogenes and muscle differentiation: multiple mechanisms of interference.

In vitro transformation of replicating myogenic cells by a variety of oncogenes is always accompanied by inhibition of the transition to the terminally differentiated state. Three main levels of interference by oncogenes may ultimately prevent transcription of skeletal muscle-specific genes. First, the transcription of muscle-regulatory factors (MRF) of the MyoD family can be extinguished in transformed myoblasts. Second, several oncoproteins are capable of silencing the transcriptional capacity of MRF. Third, the DNA binding activity of MRF can be negatively modulated by phosphorylation or competition by dominant negative partners. Oncogenes can function at multiple potential levels of regulation, depending on the myogenic cell context.