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Resveratrol-induced activation of p53 and apoptosis is mediated by extracellular-signal-regulated protein kinases and p38 kinase.
She, Q B; Bode, A M; Ma, W Y; Chen, N Y; Dong, Z.
Afiliação
  • She QB; The Hormel Institute, University of Minnesota, Austin 55912, USA.
Cancer Res ; 61(4): 1604-10, 2001 Feb 15.
Article em En | MEDLINE | ID: mdl-11245472
ABSTRACT
Resveratrol, a phytoalexin found in grapes, berries, and peanuts, is one of the most promising agents for cancer prevention. Our previous study showed that the antitumor activity of resveratrol occurs through p53-mediated apoptosis. In this study, we have elucidated the potential signaling components underlying resveratrol-induced p53 activation and induction of apoptosis. We found that in a mouse JB6 epidermal cell line, resveratrol activated extracellular-signal-regulated protein kinases (ERKs), c-Jun NH2-terminal kinases (JNKs), and p38 kinase and induced serine 15 phosphorylation of p53. Stable expression of a dominant negative mutant of ERK2 or p38 kinase or their respective inhibitor, PD98059 or SB202190, repressed the phosphorylation of p53 at serine 15. In contrast, overexpression of a dominant negative mutant of JNKI had no effect on the phosphorylation. Most importantly, ERKs and p38 kinase formed a complex with p53 after treatment with resveratrol. Strikingly, resveratrol-activated ERKs and p38 kinase, but not JNKs, phosphorylated p53 at serine 15 in vitro. Furthermore, pretreatment of the cells with PD98059 or SB202190 or stable expression of a dominant negative mutant of ERK2 or p38 kinase impaired resveratrol-induced p53-dependent transcriptional activity and apoptosis, whereas constitutively active MEK1 increased the transcriptional activity of p53. These data strongly suggest that both ERKs and p38 kinase mediate resveratrol-induced activation of p53 and apoptosis through phosphorylation of p53 at serine 15.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Estilbenos / Proteína Supressora de Tumor p53 / Anticarcinógenos / Apoptose / Proteínas Quinases Ativadas por Mitógeno Limite: Animals Idioma: En Revista: Cancer Res Ano de publicação: 2001 Tipo de documento: Article País de afiliação: Estados Unidos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Estilbenos / Proteína Supressora de Tumor p53 / Anticarcinógenos / Apoptose / Proteínas Quinases Ativadas por Mitógeno Limite: Animals Idioma: En Revista: Cancer Res Ano de publicação: 2001 Tipo de documento: Article País de afiliação: Estados Unidos