P53-INDEPENDENT EXPRESSION OF P21(CIP)1 IN MUSCLE AND OTHER TERMINALLY DIFFERENTIATING CELLS

Terminal differentiation is coupled to withdrawal from the cell cycle. The cyclin-dependent kinase inhibitor (CKI) p21(Cip1) is transcriptio nally regulated by p53 and can induce growth arrest. CKIs are therefor e potential mediators of developmental control of cell proliferation. The expression pattern of mouse p21 correlated with terminal different iation 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 p2 1 expression in 10T1/2 cells, p21 was expressed in myogenic cells of m ice lacking the genes encoding MyoD and myogenin, demonstrating that p 21 expression does not require these transcription factors. The p21 pr otein may function during development as an inducible growth inhibitor that contributes to cell cycle exit and differentiation.