title: Differential regulation of jun family gene expression by the tumor promoter okadaic acid.
abstract: Phosphorylation events are major regulatory mechanisms of signal transduction pathways that control cell growth and differentiation. The potential involvement of serine/threonine-specific phosphoprotein phosphatases in pathways that regulate gene expression was analyzed. By use of okadaic acid, an inhibitor of protein phosphatases 1 (PP-1) and 2A (PP-2A), we present evidence that expression of distinct members of the jun family of genes, c-jun, junB, and junD, are regulated differentially by serine/threonine-specific phosphoprotein phosphatases. Treatment of cells with okadaic acid induces the expression of junB, and to a lesser extent c-jun, but has only a marginal effect on junD expression. This induction involves transcriptional as well as post-transcriptional mechanisms. An analysis of defined elements in different promoters suggests that serine/threonine phosphoprotein phosphatases are involved in the regulation of the c-jun and the collagenase 12-O-tetradecanoyl phorbol-13-acetate (TPA) response element (TRE) as well as the c-fos serum response element (SRE). Since inhibition of PP-1 and PP-2A leads to increased proto-oncogene expression, our results further support the view that certain protein phosphatases might act as negative regulators of growth.
authors.affiliation: Cancer Center, University of California, San Diego, La Jolla 92093-0636.
authors.forename: A
authors.initials: A
authors.lastname: Schönthal
authors.forename: A S
authors.initials: AS
authors.lastname: Alberts
authors.forename: J A
authors.initials: JA
authors.lastname: Frost
authors.forename: J R
authors.initials: JR
authors.lastname: Feramisco
mesh_terms: D016475:3T3 Cells / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002273:Carcinogens / Q000494:pharmacology*; D004268:DNA-Binding Proteins; D004357:Drug Synergism; D004988:Ethers, Cyclic / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D051379:Mice; D003012:Microbial Collagenase / Q000235:genetics; D008969:Molecular Sequence Data; D005810:Multigene Family; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000502:physiology*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis / Q000235:genetics*; D011519:Proto-Oncogenes / Q000187:drug effects*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012045:Regulatory Sequences, Nucleic Acid; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D002273:Carcinogens; D004268:DNA-Binding Proteins; D004988:Ethers, Cyclic; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011993:Recombinant Fusion Proteins; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases; D003012:Microbial Collagenase; D013755:Tetradecanoylphorbol Acetate