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

초록

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-Ras(G12V)-induced P27(Kip1) down-regulation. JNK siRNA treatment also promoted recovery from the H-Ras(G12V)-induced p27(Kip1) down-regulation. 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 RASSFIA exerts a tumor-suppressing effect by blocking oncogenic Ras-induced JNK activation.

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