p53-Independent Expression of p21 ^Cip1 in Muscle and Other Terminally Differentiating Cells

TLDR

Terminal differentiation involves cell cycle exit, and the cyclin‑dependent kinase inhibitor p21, regulated by p53, serves as a key growth‑arrest mediator that may contribute to developmental control of proliferation. Mouse p21 is expressed during terminal differentiation of several lineages—including muscle, cartilage, skin, and nasal epithelium—independently of p53 and of the myogenic transcription factors MyoD and myogenin.

Abstract

Terminal differentiation is coupled to withdrawal from the cell cycle. The cyclin-dependent kinase inhibitor (CKI) p21 Cip1 is transcriptionally regulated by p53 and can induce growth arrest. CKIs are therefore potential mediators of developmental control of cell proliferation. The expression pattern of mouse p21 correlated with terminal differentiation of multiple cell lineages including skeletal muscle, cartilage, skin, and nasal epithelium in a p53-independent manner. Although the muscle-specific transcription factor MyoD is sufficient to activate p21 expression in 10T1/2 cells, p21 was expressed in myogenic cells of mice lacking the genes encoding MyoD and myogenin, demonstrating that p21 expression does not require these transcription factors. The p21 protein may function during development as an inducible growth inhibitor that contributes to cell cycle exit and differentiation.