Correlation of Terminal Cell Cycle Arrest of Skeletal Muscle with Induction of p21 by MyoD

TLDR

Skeletal muscle differentiation involves coordinated gene expression and terminal withdrawal from the cell cycle, a G0 arrest that depends on the retinoblastoma protein whose activity is negatively regulated by cyclin‑dependent kinases and their inhibitors. MyoD may induce terminal cell cycle arrest during skeletal muscle differentiation by increasing the expression of p21. MyoD activates the Cdk inhibitor p21 in differentiating myocytes and nonmyogenic cells, a p53‑independent induction that correlates with cell cycle withdrawal.

Abstract

Skeletal muscle differentiation entails the coordination of muscle-specific gene expression and terminal withdrawal from the cell cycle. This cell cycle arrest in the G0 phase requires the retinoblastoma tumor suppressor protein (Rb). The function of Rb is negatively regulated by cyclin-dependent kinases (Cdks), which are controlled by Cdk inhibitors. Expression of MyoD, a skeletal muscle-specific transcriptional regulator, activated the expression of the Cdk inhibitor p21 during differentiation of murine myocytes and in nonmyogenic cells. MyoD-mediated induction of p21 did not require the tumor suppressor protein p53 and correlated with cell cycle withdrawal. Thus, MyoD may induce terminal cell cycle arrest during skeletal muscle differentiation by increasing the expression of p21.