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

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-Ras ^G12V induced JNK phosphorylation and RASSF1A co-transfected with H-Ras^G12V efficiently suppressed Ras-triggered JNK activation in various cancer cell lines. RASSF1A expression revived the H-Ras ^G12V-induced p27^Kip1 down-regulation. JNK siRNA treatment also promoted recovery from the H-Ras^G12V-induced p27^Kip1 downregulation. These results demonstrate that RASSF1A inhibited H-Ras ^G12V-induced JNK activation and JNK-mediated p27^Kip1 down-regulation. From these results, we propose that RASSF1A exerts a tumor-suppressing effect by blocking oncogenic Ras-induced JNK activation.