Early G sub(1) growth arrest of hybridoma B cells by DMSO involves cyclin D2 inhibition and p21 super([CIP1]) induction

Dimethylsulfoxide (DMSO) was shown to inhibit the proliferation of several B cell lines including Raji, Daudi, and SKW6-CL4 but the mechanisms involved in this growth arrest are still unclear. We show that in 7TD1 mouse hybridoma cells a DMSO-induced reversible G sub(1) arrest involves inactivation of Rb kinases, cyclin D2/CDK4 and cyclin E/CDK2. This occurs by at least three distinct mechanisms. Inhibition of cyclin D2 neosynthesis leads to a dramatic decrease of cyclinD2/CDK4 complexes. This in turn enables the redistribution of p27 super([KIP1]) from cyclin D2/CDK4 to cyclin E/CDK2 complexes. In addition, the simultaneous accumulation of p21 super([CIP1]) entails increasing association with cyclin D3/CDK4 and cyclin E/CDK2. Thus, p21 super([CIP1]) and p27 super([KIP1]), act in concert to inhibit cyclin E/CDK2 activity which, together with CDK4 inactivation, confers a G sub(1)-phase arrest.