p12(DOC-1) is a novel cyclin-dependent kinase 2-associated protein.
Mol Cell Biol
; 20(17): 6300-7, 2000 Sep.
Article
em En
| MEDLINE
| ID: mdl-10938106
ABSTRACT
Regulated cyclin-dependent kinase (CDK) levels and activities are critical for the proper progression of the cell division cycle. p12(DOC-1) is a growth suppressor isolated from normal keratinocytes. We report that p12(DOC-1) associates with CDK2. More specifically, p12(DOC-1) associates with the monomeric nonphosphorylated form of CDK2 (p33CDK2). Ectopic expression of p12(DOC-1) resulted in decreased cellular CDK2 and reduced CDK2-associated kinase activities and was accompanied by a shift in the cell cycle positions of p12(DOC-1) transfectants ( upward arrow G(1) and downward arrow S). The p12(DOC-1)-mediated decrease of CDK2 was prevented if the p12(DOC-1) transfectants were grown in the presence of the proteosome inhibitor clasto-lactacystin beta-lactone, suggesting that p12(DOC-1) may target CDK2 for proteolysis. A CDK2 binding mutant was created and was found to revert p12(DOC-1)-mediated, CDK2-associated cell cycle phenotypes. These data support p12(DOC-1) as a specific CDK2-associated protein that negatively regulates CDK2 activities by sequestering the monomeric pool of CDK2 and/or targets CDK2 for proteolysis, reducing the active pool of CDK2.
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MEDLINE
Assunto principal:
Proteínas
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Proteínas Serina-Treonina Quinases
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Quinases Ciclina-Dependentes
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Proteínas Supressoras de Tumor
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Quinases relacionadas a CDC2 e CDC28
Idioma:
En
Ano de publicação:
2000
Tipo de documento:
Article