title: c-Myb negatively regulates Ras signaling through induction of dual phosphatase MKP-3 in NIH3T3 cells.
abstract: Mitogen-activated protein kinase phosphatase-3 (MKP-3) negatively regulates ERK1/2 MAPK in a feedback loop. However, little is known about the molecular mechanism by which Ras signaling induces MKP-3 expression. In the present study, we demonstrate that exogenous expression of constitutively active H-Ras increases the level of MKP-3 mRNA. A transfection study using a series of MKP-3 promoter deletion constructs revealed that the c-Myb binding site is required for Ras-induced transcriptional activation of the MKP-3 gene promoter. Furthermore, we show that c-Myb directly binds to the MKP-3 promoter, as revealed by electrophoretic mobility shift assay and chromatin immunoprecipitation. Knock-down of c-Myb expression using siRNA abrogated Ras-induced MKP-3 promoter activity. These findings propose a novel mechanism through which Ras signaling activates c-Myb-dependent transcriptional activation of the MKP-3 gene.
authors: School of Life Science and Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors: Young Jae
authors: YJ
authors: Park
authors: Department of Biological Sciences, College of Biological Science and Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
authors: Jong Min
authors: JM
authors: Lee
authors: Department of Biological Sciences, College of Biological Science and Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
authors: Mi So
authors: MS
authors: Lee
authors: School of Life Science and Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea. Electronic address: ykim@knu.ac.kr.
authors: Young Ho
authors: YH
authors: Kim
authors: Department of Biological Sciences, College of Biological Science and Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea. Electronic address: shinsy@konkuk.ac.kr.
authors: Soon Young
authors: SY
authors: Shin
mesh_terms: D000818:Animals; D054642:Dual Specificity Phosphatase 6 / Q000096:biosynthesis* / Q000235:genetics; D004790:Enzyme Induction; D051379:Mice; D041681:NIH 3T3 Cells; D011401:Promoter Regions, Genetic; D020598:Proto-Oncogene Proteins c-myb / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic; D015854:Up-Regulation; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D020598:Proto-Oncogene Proteins c-myb; D054642:Dual Specificity Phosphatase 6; C517036:Dusp6 protein, mouse; D018631:ras Proteins
keywords: ERK; H-Ras; MKP-3; NIH3T3 fibroblasts; c-Myb