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.
Liu
Z J
ZJ
Department of Biochemistry, Kobe University School of Medicine, Chuo-ku, Kobe 650, Japan. liuzj@med.kobe-u.ac.jp
Ueda
T
T
Miyazaki
T
T
Tanaka
N
N
Mine
S
S
Tanaka
Y
Y
Taniguchi
T
T
Yamamura
H
H
Minami
Y
Y
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D016203:CDC2 Protein Kinase / Q000096:biosynthesis / Q000235:genetics; D002453:Cell Cycle / Q000502:physiology*; D002478:Cells, Cultured; D056745:Cyclin C; D056743:Cyclin D3; D019927:Cyclin E / Q000378:metabolism; D018844:Cyclin-Dependent Kinases; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D007377:Interleukin-3 / Q000378:metabolism; D007399:Interphase; D051379:Mice; D008938:Mitosis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic
C503674:CCNC protein, human; C534696:CCND3 protein, human; C503675:Ccnc protein, mouse; C534697:Ccnd3 protein, mouse; D056745:Cyclin C; D056743:Cyclin D3; D019927:Cyclin E; D016213:Cyclins; D007377:Interleukin-3; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D018844:Cyclin-Dependent Kinases