title: Expression of immediate early gene pip92 during anisomycin-induced cell death is mediated by the JNK- and p38-dependent activation of Elk1.
abstract: We report here that immediate early gene pip92 is expressed during anisomycin-induced cell death in fibroblast NIH3T3 cells. To determine the mechanism by which this occurs and to identify downstream signaling pathways, we investigated the induction of the pip92 promoter. The activation of pip92 by anisomycin is mediated by the activation of MAP kinases, such as JNK and p38 kinase, but not ERK. Deletion analysis of the pip92 promoter indicated that pip92 activation occurs primarily within the region containing a serum response element (SRE). Further analysis of the SRE using a heterologous thymidine kinase promoter showed that both an Ets and CArG-like site are required for anisomycin-induced pip92 expression. Elk1, which binds to the Ets site, was phosphorylated by the JNK- and p38-dependent pathways and the phosphorylation of Elk1-GAL4 fusion proteins by these pathways was sufficient for the transactivation. Overall, this study suggested that different MAPK pathways are involved in the expression of immediate early gene pip92 by growth factors and environmental stresses.
authors.affiliation: Department of Pharmacology and Brain Research Institute, Yonsei University College of Medicine, Seoul, Korea. kchung@yumc.yonsei.ac.kr
authors.forename: K C
authors.initials: KC
authors.lastname: Chung
authors.forename: S M
authors.initials: SM
authors.lastname: Kim
authors.forename: S
authors.initials: S
authors.lastname: Rhang
authors.forename: L F
authors.initials: LF
authors.lastname: Lau
authors.forename: I
authors.initials: I
authors.lastname: Gomes
authors.forename: Y S
authors.initials: YS
authors.lastname: Ahn
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000841:Anisomycin / Q000494:pharmacology*; D015152:Blotting, Northern; D016923:Cell Death / Q000187:drug effects*; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D004268:DNA-Binding Proteins; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005656:Fungal Proteins / Q000378:metabolism; D017353:Gene Deletion; D017874:Immediate-Early Proteins; D051379:Mice; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D015221:Potassium Channels / Q000378:metabolism*; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011506:Proteins / Q000502:physiology; D011518:Proto-Oncogene Proteins; D012313:RNA / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction; D013937:Thymidine Kinase / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection; D050807:ets-Domain Protein Elk-1; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D004268:DNA-Binding Proteins; C494113:Elk1 protein, mouse; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; D017874:Immediate-Early Proteins; D015221:Potassium Channels; D011500:Protein Synthesis Inhibitors; D011506:Proteins; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; C066505:Ier2 protein, mouse; D012313:RNA; D000841:Anisomycin; D015500:Chloramphenicol O-Acetyltransferase; D013937:Thymidine Kinase; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases