title: Deregulated repression of c-Jun provides a potential link to its role in tumorigenesis.
abstract: The transcription factor c-Jun cooperates with oncogenic alleles of ras in malignant transformation. Constitutively active Ras causes, via activation of mitogen activated protein kinases, phosphorylation of c-Jun which is essential for subsequent target gene activation and tumorigenesis. Studying the mechanisms controlling c-Jun activity we found that its transcription activation function is actively repressed by a presumably multimeric repressor complex that includes histone deacetylase 3 as a critical subunit. Suppression of c-Jun is relieved by MAP kinase-mediated phosphorylation and/or titration of inhibitor components. The viral tumorigenic counterpart of c-Jun, v-Jun, escapes this inhibition, suggesting deregulated transcriptional activity of c-Jun as a relevant cause for carcinogenesis.
authors.affiliation: Institute of Toxicology, University of Mainz, Mainz, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Weiss
authors.forename: Dirk
authors.initials: D
authors.lastname: Bohmann
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D016758:Genes, jun / Q000502:physiology*; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D010766:Phosphorylation; D012097:Repressor Proteins / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics / Q000502:physiology; D018631:ras Proteins / Q000378:metabolism; D000099186:Histone Deacetylase 3
chemical_list: D006655:Histone Deacetylases; D020929:Mitogen-Activated Protein Kinase Kinases; D012097:Repressor Proteins; D018631:ras Proteins; D000099186:Histone Deacetylase 3