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Biochemical characterization of p16INK4- and p18-containing complexes in human cell lines.
Ragione, F D; Russo, G L; Oliva, A; Mercurio, C; Mastropietro, S; Pietra, V D; Zappia, V.
Afiliação
  • Ragione FD; Institute of Biochemistry of Macromolecules, Medical School, Second University of Naples, Italy.
J Biol Chem ; 271(27): 15942-9, 1996 Jul 05.
Article em En | MEDLINE | ID: mdl-8663131
The regulation of the D-type cyclin-dependent kinase (CDK4 and CDK6) activity appears to be the key step in the progression of eukaryotic cells through the G1 cell cycle phase. One of the mechanisms involved in this process is the binding of some small proteic inhibitors, with a molecular mass ranging between 14 and 20 kDa, to these CDKs. We have evaluated the amount of two such inhibitors, namely p16(INK4) and p18, in normal and transformed cells, as well as the biochemical features of the macromolecular complexes containing these proteins. The results obtained indicated that (i) p18 gene expression, unlike p16(INK4) gene, is not regulated by pRb status, (ii) no evident relationship exists between the expression of p16(INK4) and p18 genes, (iii) significant amounts of the two proteins are not bound to CDKs but occur as free molecules, (iv) each inhibitor forms a complex with the CDK protein with a 1:1 stoichiometry, and (v) a competition exists between cyclin D and the inhibitor protein toward the CDK protein resulting in the absence of detectable cellular free kinase. Moreover, employing the human native partially purified p16(INK4)or the pure recombinant protein, we have been able to demonstrate in vitro the dissociation of CDK4-cyclin D1 complex and the formation of CDK4-p16(INK4) bimolecular complex. Our findings suggest that during the cell division cycle the members of the p16(INK4) protein family and cyclin Ds compete for binding to CDK4/CDK6 and that their quantitative ratio is essential for G1 --> S transition.
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Coleções: 01-internacional Contexto em Saúde: 3_ND Base de dados: MEDLINE Assunto principal: Proteínas de Transporte / Proteína do Retinoblastoma / Proteínas Proto-Oncogênicas / Proteínas de Ciclo Celular / Proteínas Supressoras de Tumor / Inibidores Enzimáticos Limite: Humans Idioma: En Revista: J Biol Chem Ano de publicação: 1996 Tipo de documento: Article
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Coleções: 01-internacional Contexto em Saúde: 3_ND Base de dados: MEDLINE Assunto principal: Proteínas de Transporte / Proteína do Retinoblastoma / Proteínas Proto-Oncogênicas / Proteínas de Ciclo Celular / Proteínas Supressoras de Tumor / Inibidores Enzimáticos Limite: Humans Idioma: En Revista: J Biol Chem Ano de publicação: 1996 Tipo de documento: Article