HTLV-1 Tax protein interacts with cyclin-dependent kinase inhibitor p16Ink4a and counteracts its inhibitory activity to CDK4.
Leukemia
; 11 Suppl 3: 14-6, 1997 Apr.
Article
em En
| MEDLINE
| ID: mdl-9209282
ABSTRACT
Tax, a regulatory protein of HTLV-1, is an oncoprotein which immortalizes human T-cells and induces tumors in transgenic mice. Here, we found that Tax binds to a cyclin-dependent kinase inhibitor, p16Ink4a. p16Ink4a binds to cyclin-dependent kinases, CDK4 and CDK6, and inhibits their activity, resulting in suppression of G1 phase progression. The binding of Tax to p16Ink4a induced a reduction of p16Ink4a/CDK4 complex, with subsequent activation of CDK4 kinase. Tax also suppressed p16Ink4a-mediated inhibition of cell growth. The p16Ink4a gene was frequently deleted in many T-cell lines, but not in HTLV-1-infected T-cell lines. Taking these findings together, the functional inactivation of p16Ink4a by Tax through protein-protein interaction is suggested to contribute to cellular immortalization and transformation by HTLV-1.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vírus Linfotrópico T Tipo 1 Humano
/
Proteínas de Transporte
/
Produtos do Gene tax
/
Proteínas Proto-Oncogênicas
/
Quinases Ciclina-Dependentes
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Leukemia
Assunto da revista:
HEMATOLOGIA
/
NEOPLASIAS
Ano de publicação:
1997
Tipo de documento:
Article
País de afiliação:
Japão