Involvement of c‐jun NH₂‐terminal kinases in resveratrol‐induced activation of p53 and apoptosis

Citations Over TimeTop 10% of 2002 papers

Abstract

Resveratrol, a constituent of grapes and other foods, is one of the most promising agents for cancer prevention. In a previous study, we showed that the antitumor activity of resveratrol occurs through extracellular signal-regulated protein kinases (ERKs) and p38 kinase-mediated p53 activation. In this study, we also determined that c-jun NH(2)-terminal kinases (JNKs) are involved in resveratrol-induced p53 activation and induction of apoptosis. In the JB6 mouse epidermal cell line, resveratrol activated JNKs dose-dependently within a dose range of 10-40 microM, the same dosage responsible for the inhibition of tumor promoter-induced cell transformation. Stable expression of a dominant negative mutant of JNK1 or disruption of the Jnk1 or Jnk2 gene markedly inhibited resveratrol-induced p53-dependent transcription activity and induction of apoptosis. Furthermore, resveratrol-activated JNKs were shown to phosphorylate p53 in vitro, but this activity was repressed in the cells expressing a dominant negative mutant of JNK1 or in Jnk1 or Jnk2 knockout (Jnk1(-/-) or Jnk2(-/-)) cells. These data suggested that JNKs act as mediators of resveratrol-induced activation of p53 and apoptosis, which may occur partially through p53 phosphorylation.

Related Papers

• → Serum starvation induces H2AX phosphorylation to regulate apoptosis via p38 MAPK pathway(2008)87 cited
• → MAPKs and Mst1/Caspase-3 pathways contribute to H2B phosphorylation during UVB-induced apoptosis(2010)13 cited
• → Teratogen‐induced activation of ERK, JNK, and p38 MAP kinases in early postimplantation murine embryos(2000)2 cited
• Effect of angiotensin II on phosphorylation of p38 Mitogen-activated protein kinases in HUVECs(2010)
• → Effect of Angiotensin III on ERK1/2 and p38 mitogen activated protein (MAP) kinases in Wistar rat VSMCs(2015)