title: RASSF1A suppresses oncogenic H-Ras-induced c-Jun N-terminal kinase activation.
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.
authors.affiliation: Graduate School of Medicine, Korea University College of Medicine, Korea University, Seoul 136-705, Korea.
authors.forename: Young A
authors.initials: YA
authors.lastname: Yoo
authors.forename: Ah Ram
authors.initials: AR
authors.lastname: Na
authors.forename: Myeong-Sok
authors.initials: MS
authors.lastname: Lee
authors.forename: Sukjoon
authors.initials: S
authors.lastname: Yoon
authors.forename: Jun Suk
authors.initials: JS
authors.lastname: Kim
authors.forename: Young Do
authors.initials: YD
authors.lastname: Yoo
mesh_terms: 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
chemical_list: 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