MUSCLE LIM PROTEIN, A NOVEL ESSENTIAL REGULATOR OF MYOGENESIS, PROMOTES MYOGENIC DIFFERENTIATION

Muscle LIM protein (MLP) is a novel positive regulator of myogenesis. Its expression and that of its Drosophila homolog DMLP1 are enriched i n striated muscle and coincide with myogenic differentiation. in the a bsence of MLP, induced C2 cells express myogenin but fail to exit from the cell cycle and to differentiate. Overexpression of MLP in C2 myob lasts potentiates myogenic differentiation and reduces its sensitivity to TGF beta. Like MLP, single LIM domain deletion mutants of MLP and nonmuscle LIM-only proteins promote myogenic differentiation. In 3T3 f ibroblasts, the same LIM proteins prevent phorbol ester-induced inhibi tion of DNA replication. These results establish MLP as an essential p romoter of myogenesis and suggest that LIM-only proteins act via simil ar mechanisms to regulate aspects of cell differentiation.