A single cdk inhibitor, p27(xic1), functions beyond cell cycle regulation to promote muscle differentiation in Xenopus

The molecular basis of the antagonism between cellular proliferation and differentiation is poorly understood. We have investigated the role of the cyclin-dependent kinase inhibitor p27(Xic1) in the co-ordination of cell cycle exit and differentiation during early myogenesis in vivo using Xenopus embryos. In this report, we demonstrate that p27(Xic1) is highly expressed in the developing myotome, that ablation of p27(Xic1) protein prevents muscle differentiation and that p27(Xic1) synergizes with the transcription factor MyoD to promote muscle differentiation. Furthermore, the ability of p27(Xic1) to promote myogenesis resides in an N-terminal domain and is separable from its cell cycle regulation function. This data demonstrates that a single cyclin-dependent kinase inhibitor, p27(Xic1), controls in vivo muscle differentiation in Xenopus and that regulation of this process by p27(Xic1) requires activities beyond cell cycle inhibition.