A critical role for cyclin C in promotion of the hematopoietic cell cycle by cooperation with c-Myc

Cyclin C, a putative G₁ cyclin, was originally isolated through its ability to complement a Saccharomyces cerevisiae strain lacking the G₁ cyclin gene CLN1-3. Unlike cyclins D1 and E, the other two G₁ cyclins obtained by the same approach and subsequently shown to play important roles during the G₁/S transition, there is thus far no evidence to support the hypothesis that cyclin C is indeed critical for the promotion of cell cycle progression. In BAF-B03 cells, an interleukin 3 (IL-3)-dependent murine pro- B-cell line, cyclin C gene mRNA was induced at the G₁/S phase upon IL-3 stimulation and reached a maximal level in the S phase. Enforced expression of exogenous cyclin C in this cell line failed to alter its growth properties. In the present study, we examined whether cyclin C is capable of cooperating with the cytokine-responsive immediate-early gene products c-Myc and c-Fos in the promotion of cell proliferation. We found that cyclin C is able to cooperate functionally with c-Myc, but not c-Fos, to induce both BAF- B03 cell proliferation in a cytokine-independent fashion and the formation of cell clusters. Furthermore, cyclin C was primarily responsible for the induction of cdc2 gene expression. Our data define a novel role for cyclin C in the regulation of both the G₁/S and G₂/M phases of the cell cycle, and this effect appears to be independent of the activity of CDK8 in the control of transcription.