Reversal of Terminal Differentiation Mediated by p107 in Rb -/- Muscle Cells

The terminal differentiation of mammalian muscle cells requires the tumor suppressor retinoblastoma protein (Rb). Unlike their wild-type counterparts, multinucleated myotubes from mouse cells deficient in Rb (Rb -/- ) were induced by serum to reenter the cell cycle. Development of the myogenic phenotype in Rb -/- cells correlated with increased expression of p107, which interacted with myogenic transcription factors. Serum-induced cell cycle reentry, on the other hand, correlated with decreased p107 expression. Thus, although p107 could substitute for Rb as a cofactor for differentiation, it could not maintain the terminally differentiated state in Rb -/- myotubes.