Kaposi sarcoma-associated viral cyclin K overrides cell growth inhibition mediated by oncostatin M through STAT3 inhibition.
Blood
; 101(10): 4070-7, 2003 May 15.
Article
em En
| MEDLINE
| ID: mdl-12531804
ABSTRACT
DNA viruses have evolved a number of mechanisms to inhibit the major cellular tumor-suppressor pathways. Viral oncogenes can override growth suppressive signals and extend the virus proliferative capacity. The Kaposi sarcoma-associated human herpesvirus 8 (KSHV) encodes a protein, cyclin K, that is similar to cellular cyclin D1 but behaves atypically. Cyclin K resists the actions of the p16 INK4a and p27Kip1 inhibitors and extends the range of cdk6 substrates, thereby inducing cell-cycle progression toward S phase. In this study, we show that cyclin K overrides growth suppressive signals through signal transducer and activator of transcription 3 (STAT3) inactivation. Cyclin K was found to associate with the activation domain of STAT3 to inhibit its DNA-binding and transcriptional activities. Overexpression of cyclin K and inhibition of STAT3 prevents the growth suppressive effect imposed by the interleukin 6-type cytokine, oncostatin M. Altogether, these results suggest that KSHV is able to override growth suppressive effects through multiple mechanisms, and they further indicate that cyclin K plays an important role in the oncogenic activity of these viruses.
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Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Sarcoma de Kaposi
/
Proteínas Virais
/
Transativadores
/
Ciclinas
/
Herpesvirus Humano 8
/
Proteínas de Ligação a DNA
/
Inibidores do Crescimento
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article