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Mol Cell Biol, June 1998, p. 3445-3454, Vol. 18, No. 6
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

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

Zhao-Jun Liu,1,* Takahiro Ueda,1 Tadaaki Miyazaki,2 Nobuyuki Tanaka,2 Shinichiro Mine,3 Yoshiya Tanaka,3 Tadatsugu Taniguchi,2 Hirohei Yamamura,1 and Yasuhiro Minami1

Department of Biochemistry, Kobe University School of Medicine, Chuo-ku, Kobe 650,1 Department of Immunology, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113,2 and First Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, Kitakyushu 807,3 Japan

Received 19 November 1997/Returned for modification 2 February 1998/Accepted 25 March 1998

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.

* Corresponding author. Mailing address: Department of Biochemistry, Kobe University School of Medicine, 7-5-1, Kusunoki-chou, Chuo-ku, Kobe 650, Japan. Phone: 81-78-3417451, ext. 3251. Fax: 81-78-3718734. E-mail: liuzj{at}med.kobe-u.ac.jp.

Mol Cell Biol, June 1998, p. 3445-3454, Vol. 18, No. 6
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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