A Critical Role for Cyclin C in Promotion of the Hematopoietic Cell Cycle by Cooperation with c-Myc

Abstract

ABSTRACT 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 cyclins obtained by the same approach and subsequently shown to play important roles during the G 1 /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 G 1 /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 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.