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Cdk6-cyclin D3 complex evades inhibition by inhibitor proteins and uniquely controls cell's proliferation competence

Oncogene volume 20, pages 2000–2009 (2001)Cite this article

Abstract

Mammalian cells require a cyclin D-dependent kinase for the cell cycle start, yet many mesenchymal cells express three seemingly redundant D cyclins and similarly, seemingly redundant Cdk4 and Cdk6 as their kinase partners. We have found that the Cdk6-cyclin D3 complex is unique among the D cyclin and kinase combinations in the ability to promote the cell cycle start. In an anchorage-minus G1-arrested rat fibroblast, only Cdk6-D3 retains kinase activity due mainly to its ability to evade inhibition by p27KIP1 and p21CIP1 with a resemblance to viral cyclin-bound Cdk6. Rodent fibroblasts engineered to overexpress both Cdk6 and cyclin D3 highly resist serum starvation- or cell–cell contact-imposed G1-arrest. In BALB/c 3T3 cells, D3 is constitutively expressed, but Cdk6 is markedly induced with concomitant activation upon stimulation with a growth-promoting factor. These results suggest a role for the Cdk6-D3 complex in regulating cell's proliferation ability in response to external stimuli.

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Acknowledgements

We thank J Kato for the mouse cyclin D3 cDNA and M Nakanish for GST-fused p27KIP1. This work was supported by grants from the Ministry of Education and Culture, Japan.

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  1. Department of Biochemistry and Molecular Biology, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

    Jie Lin, Shigeki Jinno & Hiroto Okayama

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  1. Jie Lin
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  2. Shigeki Jinno
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Lin, J., Jinno, S. & Okayama, H. Cdk6-cyclin D3 complex evades inhibition by inhibitor proteins and uniquely controls cell's proliferation competence. Oncogene 20, 2000–2009 (2001). https://doi.org/10.1038/sj.onc.1204375

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