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-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.
Yoo
Young A
YA
Graduate School of Medicine, Korea University College of Medicine, Korea University, Seoul 136-705, Korea.
Na
Ah Ram
AR
Lee
Myeong-Sok
MS
Yoon
Sukjoon
S
Kim
Jun Suk
JS
Yoo
Young Do
YD
D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D004789:Enzyme Activation; D011905:Genes, ras; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D018631:ras Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism
D050759:Cyclin-Dependent Kinase Inhibitor p21; C411762:RASSF1 protein, human; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; D048670:MAP Kinase Kinase 4; D018631:ras Proteins