A CRITICAL ROLE FOR CYCLIN-C IN PROMOTION OF THE HEMATOPOIETIC-CELL CYCLE BY COOPERATION WITH C-MYC

Cyclin C, a putative G(1) cyclin, was originally isolated through its ability to complement a Saccharomyces cerevisiae strain lacking the G( 1) cyclin gene CLN1-3. Unlike cyclins D1 and E, the other two G(1) cyc lins obtained by the same approach and subsequently shown to play impo rtant roles during the G(1)/S transition, there is thus far no evidenc e to support the hypothesis that cyclin C is indeed critical for the p romotion of cell cycle progression. In BAF-B03 cells, an interleukin 3 (IL-3)-dependent murine pro-B-cell line, cyclin C gene mRNA was induc ed at the G(1)/S phase upon IL-3 stimulation and reached a maximal lev el in the S phase. Enforced expression of exogenous cyclin C in this c ell line failed to alter its growth properties. In the present study, we examined whether cyclin C is capable of cooperating with the cytoki ne-responsive immediate-early gene products c-Myc and c-Fos in the pro motion of cell proliferation. We found that cyclin C is able to cooper ate functionally with c-Myc, but not c-Fos, to induce both BAF-B03 cel l proliferation in a cytokine-independent fashion and the formation of cell clusters. Furthermore, cyclin C was primarily responsible for th e induction of cdc2 gene expression. Our data define a novel role for cyclin C in the regulation of both the G(1)/S and G(2)/M phases of the cell cycle, and this effect appears to be independent of the activity of CDK8 in the control of transcription.