CORRELATION OF TERMINAL CELL-CYCLE ARREST OF SKELETAL-MUSCLE WITH INDUCTION OF P21 BY MYOD

Skeletal muscle differentiation entails the coordination of muscle-spe cific gene expression and terminal withdrawal from the cell cycle. Thi s cell cycle arrest in the G(0) phase requires the retinoblastoma tumo r suppressor protein (Rb). The function of Rb is negatively regulated by cyclin-dependent kinases (Cdks), which are controlled by Cdk inhibi tors. Expression of MyoD, a skeletal muscle-specific transcriptional r egulator, activated the expression of the Cdk inhibitor p21 during dif ferentiation of murine myocytes and in nonmyogenic cells. MyoD-mediate d induction of p21 did not require the tumor suppressor protein p53 an d correlated with cell cycle withdrawal. Thus, MyoD may induce termina l cell cycle arrest during skeletal muscle differentiation by increasi ng the expression of p21.