RASSF1A suppresses oncogenic H-Ras-induced c-Jun N-terminal kinase activation

Int J Oncol. 2006 Dec;29(6):1541-7.

Abstract

The constitutive activation of JNK has been implicated in Ras-induced cellular transformation and activated JNK is down-regulated by the tumor suppressor protein, RASSF1A. In this study, we examined whether RASSF1A blocked oncogenic Ras-induced JNK activation. Exogenous expression of H-RasG12V induced JNK phosphorylation and RASSF1A co-transfected with H-RasG12V efficiently suppressed Ras-triggered JNK activation in various cancer cell lines. RASSF1A expression revived the H-RasG12V-induced p27Kip1 down-regulation. JNK siRNA treatment also promoted recovery from the H-RasG12V-induced p27Kip1 down-regulation. These results demonstrate that RASSF1A inhibited H-RasG12V-induced JNK activation and JNK-mediated p27Kip1 down-regulation. From these results, we propose that RASSF1A exerts a tumor-suppressing effect by blocking oncogenic Ras-induced JNK activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Enzyme Activation
  • Genes, ras*
  • Humans
  • MAP Kinase Kinase 4 / biosynthesis
  • MAP Kinase Kinase 4 / genetics
  • MAP Kinase Kinase 4 / metabolism*
  • RNA, Small Interfering / genetics
  • Transfection
  • Tumor Suppressor Proteins / biosynthesis
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • ras Proteins / biosynthesis
  • ras Proteins / genetics
  • ras Proteins / metabolism

Substances

  • Cyclin-Dependent Kinase Inhibitor p21
  • RASSF1 protein, human
  • RNA, Small Interfering
  • Tumor Suppressor Proteins
  • MAP Kinase Kinase 4
  • ras Proteins