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

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 G(1)-arrested rat fibroblast, only Cdk6-D3 retains kinase activity due mainly to its ability to evade inhibition by p27(KIP1) and p21(CIP1) 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 G(1)-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.
Mesh Terms:
3T3 Cells, Animals, Cell Adhesion, Cell Cycle Proteins, Cell Division, Contact Inhibition, Cyclin D3, Cyclin-Dependent Kinase 6, Cyclin-Dependent Kinase Inhibitor p21, Cyclin-Dependent Kinase Inhibitor p27, Cyclin-Dependent Kinases, Cyclins, G1 Phase, Mice, Mice, Inbred BALB C, Mice, Inbred C3H, Microtubule-Associated Proteins, Platelet-Derived Growth Factor, Precipitin Tests, Protein-Serine-Threonine Kinases, Rats, Tetradecanoylphorbol Acetate, Tumor Suppressor Proteins
Oncogene
Date: Apr. 12, 2001
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