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Accumulation of high levels of the p53 and p130 growth-suppressing proteins in cell lines stably over-expressing cyclin-dependent kinase 6 (cdk6)

Oncogene volume 20, pages 2889–2899 (2001)Cite this article

Abstract

Cyclin-dependent kinase 6(cdk6) is present in randomly proliferating cultures of 3T3 cells but has little detectable enzymatic activity. Significant activity is detected only during a short period in early G1 phase. To examine the possible functions of cdk6 in 3T3 cells, lines stably over-expressing cdk6 were constructed and compared to normal 3T3 cells or cell lines with reduced cdk6 levels due to expression of a dominant-negative form of the protein. Over-expression of cdk6 in cells, which led to high levels of activity even in proliferating cultures, had dramatic effects. Cell lines stably over-expressing wild-type cdk6 had a markedly reduced growth rate compared to parental 3T3 cells or lines expressing a dominant-negative form of cdk6. They also over-produced the p53 and p130 proteins and had increased sensitivity to UV-irradiation. Irradiation resulted in accumulation of the Bax protein and rapid cell death. Levels of p53 and p130 proteins were down-regulated and the growth rate of the cells was increased by introduction of the dominant-negative form of cdk6 into cells over-expressing cdk6, indicating that cdk6 is involved in the overproduction of p53 and p130. The results suggest that cdk6, through regulation of growth-suppressing molecules, may play a role in halting cellular growth when proliferation is inappropriate.

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Acknowledgements

We thank Joanne Hahn and Joseph S Lucas for expert technical assistance and helpful discussions. This research was supported in part by American Cancer Society Grant IM-746 (to JJ Lucas), by grants from the Denver Metropolitan Chapter of the Susan G Komen Breast Cancer Foundation and the Cancer League of Colorado (to JJ Lucas), by grants from the National Institute of Health HL-36577 and AI-42246 (EW Gelfand) and by the University of Colorado Cancer Center Core Grant CA46934.

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  1. Division of Basic Sciences, Department of Pediatrics, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, 80206, Colorado, CO, USA

    Masayuki Nagasawa, Erwin W Gelfand & Joseph J Lucas

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  1. Masayuki Nagasawa
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Nagasawa, M., Gelfand, E. & Lucas, J. Accumulation of high levels of the p53 and p130 growth-suppressing proteins in cell lines stably over-expressing cyclin-dependent kinase 6 (cdk6). Oncogene 20, 2889–2899 (2001). https://doi.org/10.1038/sj.onc.1204396

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