An important role for the retinoblastoma protein in staurosporine-induced G1 arrest in murine embryonic fibroblasts

In this study, we investigated the molecular basis of the ability of staurosporine to induce G(1) arrest in murine embryonic fibroblasts (MEFs), We used MEFs from transgenic mice lacking several negative regulators of the G(1)/S phase transition including cells from mice lacking p53, p21, retinoblastoma (Rb), or p16 genes. We found that p53 function was not essential for staurosporine-induced G(1) arrest. In contrast, MEFs from mice lacking Rb genes showed approximately a 70% reduced capacity to arrest in the G(1) phase following staurosporine treatment, In support of a role for Rb in staurosporine-induced G(1) arrest, rat embryonic fibroblasts stably overexpressing cyclin D1/Cdk4(R24C) exhibited approximately a 50% reduced G(1) arrest response to staurosporine. The role of Rb in determining the degree of staurosporine-induced G(1) arrest did not depend on the function of the cyclin-dependent kinase inhibitors p16 or p21 because MEFs lacking either of these genes were still capable of undergoing G(1) arrest following staurosporine exposure. Our studies provide evidence of an important role for the Rb protein in determining the degree of staurosporine-induced G(1) arrest in the first cell cycle.