title: Transcriptional and post-transcriptional regulation of c-fos expression by the tumor promoter okadaic acid.
abstract: Phosphorylation events are major regulatory mechanisms of signal transduction pathways that control cell growth and differentiation. We analyzed the potential contribution of serine/threonine specific protein phosphatases to the regulation of the c-fos gene, a proto-oncogene that is involved in the regulation of cell growth and differentiation. By use of okadaic acid, an inhibitor of protein phosphatases 1 and 2A, we present evidence that expression of the c-fos gene is regulated by serine/threonine specific protein phosphatases. This control is exerted on the transcriptional as well as the post-transcriptional level. The results suggest that dephosphorylation of regulatory phosphoproteins is an important mechanism for the down-regulation of c-fos promoter activity and the rapid degradation of c-fos mRNA. Examination of two protein kinase pathways that are known to regulate c-fos expression indicated that okadaic acid acted synergistically with protein kinase C, but not with protein kinase A. Since inhibition of serine/threonine specific phosphatases increases proto-oncogene expression, these experiments further strengthen the view that certain protein phosphatases may act as negative regulators of cell growth.
authors.affiliation: UCSD Cancer Center, University of California, La Jolla 92093.
authors.forename: A
authors.initials: A
authors.lastname: Schönthal
authors.forename: Y
authors.initials: Y
authors.lastname: Tsukitani
authors.forename: J R
authors.initials: JR
authors.lastname: Feramisco
mesh_terms: D001345:Autoradiography; D002273:Carcinogens / Q000494:pharmacology; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D004988:Ethers, Cyclic / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000187:drug effects*; D019319:Okadaic Acid; D011493:Protein Kinase C / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D002273:Carcinogens; D004988:Ethers, Cyclic; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D014157:Transcription Factors; D019319:Okadaic Acid; D011494:Protein Kinases; D011493:Protein Kinase C