Document Detail

Cdk6-cyclin D3 complex evades inhibition by inhibitor proteins and uniquely controls cell's proliferation competence.
MedLine Citation:
PMID:  11360184     Owner:  NLM     Status:  MEDLINE    
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.
J Lin; S Jinno; H Okayama
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Oncogene     Volume:  20     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  2001 Apr 
Date Detail:
Created Date:  2001-05-21     Completed Date:  2001-05-31     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  2000-9     Citation Subset:  IM    
Department of Biochemistry and Molecular Biology, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
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MeSH Terms
3T3 Cells
Cell Adhesion / physiology
Cell Cycle Proteins*
Cell Division / physiology
Contact Inhibition / physiology
Cyclin D3
Cyclin-Dependent Kinase 6
Cyclin-Dependent Kinase Inhibitor p21
Cyclin-Dependent Kinase Inhibitor p27
Cyclin-Dependent Kinases*
Cyclins / antagonists & inhibitors,  metabolism,  physiology*
G1 Phase / physiology
Mice, Inbred BALB C
Mice, Inbred C3H
Microtubule-Associated Proteins / metabolism,  physiology
Platelet-Derived Growth Factor / pharmacology
Precipitin Tests
Protein-Serine-Threonine Kinases / antagonists & inhibitors,  metabolism,  physiology*
Tetradecanoylphorbol Acetate / pharmacology
Tumor Suppressor Proteins*
Reg. No./Substance:
0/Ccnd3 protein, mouse; 0/Ccnd3 protein, rat; 0/Cdkn1a protein, mouse; 0/Cdkn1a protein, rat; 0/Cdkn1b protein, mouse; 0/Cdkn1b protein, rat; 0/Cell Cycle Proteins; 0/Cyclin D3; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/Microtubule-Associated Proteins; 0/Platelet-Derived Growth Factor; 0/Tumor Suppressor Proteins; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; 16561-29-8/Tetradecanoylphorbol Acetate; EC Kinases; EC protein, mouse; EC protein, rat; EC Kinase 6; EC Kinases

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