Okadaic acid-dependent induction of the urokinase-type plasminogen activator gene associated with stabilization and autoregulation of c-Jun

We have previously shown that the tumor promoter okadaic acid (OA), an inhibitor of protein phosphatases 1 and 2A, transcriptionally induces the urokinase-type plasminogen activator (uPA) gene in LLC-PK1 cells. This induction occurs independently of the protein kinase C- and cAMP-dependent signaling...

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Veröffentlicht in:The Journal of biological chemistry 1994-01, Vol.269 (4), p.2887-2894
Hauptverfasser: LEE, J. S, FAVRE, B, HEMMINGS, B. A, KIEFER, B, NAGAMINE, Y
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container_issue 4
container_start_page 2887
container_title The Journal of biological chemistry
container_volume 269
creator LEE, J. S
FAVRE, B
HEMMINGS, B. A
KIEFER, B
NAGAMINE, Y
description We have previously shown that the tumor promoter okadaic acid (OA), an inhibitor of protein phosphatases 1 and 2A, transcriptionally induces the urokinase-type plasminogen activator (uPA) gene in LLC-PK1 cells. This induction occurs independently of the protein kinase C- and cAMP-dependent signaling pathways. Here we show that a sequence located 2.0 kilobases upstream of the uPA gene, which resembles an AP-1-recognition sequence, mediates the action of OA. DNA-protein interaction studies, together with mRNA and protein analyses, indicate that c-Jun, but not c-Fos, is involved in OA-dependent uPA gene induction. The appearance of high levels of uPA mRNA and DNA binding activity of c-Jun to the AP-1-like site correspond to the appearance of c-Jun accumulation, suggesting that c-Jun accumulation is a critical event in OA-dependent uPA gene induction. c-Jun protein levels increase significantly between 100 and 160 min following OA treatment, whereas c-Jun translation increases only slightly in this time frame, suggesting that post-translation mechanisms are also involved in c-Jun accumulation. Pulse-chase analyses shows that OA specifically stabilizes c-Jun. We discuss our results with respect to the possibility that protein phosphatase 2A maintains c-Jun in its down-regulated state in LLC-PK1 cells.
doi_str_mv 10.1016/S0021-9258(17)42025-4
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The appearance of high levels of uPA mRNA and DNA binding activity of c-Jun to the AP-1-like site correspond to the appearance of c-Jun accumulation, suggesting that c-Jun accumulation is a critical event in OA-dependent uPA gene induction. c-Jun protein levels increase significantly between 100 and 160 min following OA treatment, whereas c-Jun translation increases only slightly in this time frame, suggesting that post-translation mechanisms are also involved in c-Jun accumulation. Pulse-chase analyses shows that OA specifically stabilizes c-Jun. 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S</creatorcontrib><creatorcontrib>FAVRE, B</creatorcontrib><creatorcontrib>HEMMINGS, B. A</creatorcontrib><creatorcontrib>KIEFER, B</creatorcontrib><creatorcontrib>NAGAMINE, Y</creatorcontrib><title>Okadaic acid-dependent induction of the urokinase-type plasminogen activator gene associated with stabilization and autoregulation of c-Jun</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>We have previously shown that the tumor promoter okadaic acid (OA), an inhibitor of protein phosphatases 1 and 2A, transcriptionally induces the urokinase-type plasminogen activator (uPA) gene in LLC-PK1 cells. This induction occurs independently of the protein kinase C- and cAMP-dependent signaling pathways. Here we show that a sequence located 2.0 kilobases upstream of the uPA gene, which resembles an AP-1-recognition sequence, mediates the action of OA. DNA-protein interaction studies, together with mRNA and protein analyses, indicate that c-Jun, but not c-Fos, is involved in OA-dependent uPA gene induction. The appearance of high levels of uPA mRNA and DNA binding activity of c-Jun to the AP-1-like site correspond to the appearance of c-Jun accumulation, suggesting that c-Jun accumulation is a critical event in OA-dependent uPA gene induction. c-Jun protein levels increase significantly between 100 and 160 min following OA treatment, whereas c-Jun translation increases only slightly in this time frame, suggesting that post-translation mechanisms are also involved in c-Jun accumulation. Pulse-chase analyses shows that OA specifically stabilizes c-Jun. 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A ; KIEFER, B ; NAGAMINE, Y</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c438t-9cdf750b7a2e7e93597492d1d08e2f556fb75d07e4eaae4c69225efab6021b613</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>8-Bromo Cyclic Adenosine Monophosphate - pharmacology</topic><topic>Animals</topic><topic>Base Sequence</topic><topic>Binding Sites</topic><topic>Biological and medical sciences</topic><topic>Blotting, Southern</topic><topic>Blotting, Western</topic><topic>Cell Line</topic><topic>Chloramphenicol O-Acetyltransferase - biosynthesis</topic><topic>Chloramphenicol O-Acetyltransferase - metabolism</topic><topic>Colchicine - pharmacology</topic><topic>Cycloheximide - pharmacology</topic><topic>DNA Mutational Analysis</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Enzyme Induction</topic><topic>Ethers, Cyclic - pharmacology</topic><topic>Fundamental and applied biological sciences. 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Rna processing</topic><topic>Transcriptional Activation</topic><topic>Transfection</topic><topic>Urokinase-Type Plasminogen Activator - biosynthesis</topic><topic>Urokinase-Type Plasminogen Activator - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>LEE, J. S</creatorcontrib><creatorcontrib>FAVRE, B</creatorcontrib><creatorcontrib>HEMMINGS, B. 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A</au><au>KIEFER, B</au><au>NAGAMINE, Y</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Okadaic acid-dependent induction of the urokinase-type plasminogen activator gene associated with stabilization and autoregulation of c-Jun</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>1994-01-28</date><risdate>1994</risdate><volume>269</volume><issue>4</issue><spage>2887</spage><epage>2894</epage><pages>2887-2894</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><coden>JBCHA3</coden><abstract>We have previously shown that the tumor promoter okadaic acid (OA), an inhibitor of protein phosphatases 1 and 2A, transcriptionally induces the urokinase-type plasminogen activator (uPA) gene in LLC-PK1 cells. This induction occurs independently of the protein kinase C- and cAMP-dependent signaling pathways. Here we show that a sequence located 2.0 kilobases upstream of the uPA gene, which resembles an AP-1-recognition sequence, mediates the action of OA. DNA-protein interaction studies, together with mRNA and protein analyses, indicate that c-Jun, but not c-Fos, is involved in OA-dependent uPA gene induction. The appearance of high levels of uPA mRNA and DNA binding activity of c-Jun to the AP-1-like site correspond to the appearance of c-Jun accumulation, suggesting that c-Jun accumulation is a critical event in OA-dependent uPA gene induction. c-Jun protein levels increase significantly between 100 and 160 min following OA treatment, whereas c-Jun translation increases only slightly in this time frame, suggesting that post-translation mechanisms are also involved in c-Jun accumulation. Pulse-chase analyses shows that OA specifically stabilizes c-Jun. We discuss our results with respect to the possibility that protein phosphatase 2A maintains c-Jun in its down-regulated state in LLC-PK1 cells.</abstract><cop>Bethesda, MD</cop><pub>American Society for Biochemistry and Molecular Biology</pub><pmid>8300623</pmid><doi>10.1016/S0021-9258(17)42025-4</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
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subjects 8-Bromo Cyclic Adenosine Monophosphate - pharmacology
Animals
Base Sequence
Binding Sites
Biological and medical sciences
Blotting, Southern
Blotting, Western
Cell Line
Chloramphenicol O-Acetyltransferase - biosynthesis
Chloramphenicol O-Acetyltransferase - metabolism
Colchicine - pharmacology
Cycloheximide - pharmacology
DNA Mutational Analysis
DNA-Binding Proteins - metabolism
Enzyme Induction
Ethers, Cyclic - pharmacology
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation, Enzymologic - drug effects
Genes, Regulator
Homeostasis
Kinetics
Marine Toxins
Molecular and cellular biology
Molecular genetics
Molecular Sequence Data
Nuclear Proteins - isolation & purification
Nuclear Proteins - metabolism
Okadaic Acid
Oligodeoxyribonucleotides - chemistry
Oligodeoxyribonucleotides - metabolism
Oxazoles - pharmacology
Phosphorylation
Protein Phosphatase 2
Protein Tyrosine Phosphatases - antagonists & inhibitors
Proto-Oncogene Proteins c-jun - biosynthesis
Proto-Oncogene Proteins c-jun - metabolism
Time Factors
Transcription. Transcription factor. Splicing. Rna processing
Transcriptional Activation
Transfection
Urokinase-Type Plasminogen Activator - biosynthesis
Urokinase-Type Plasminogen Activator - genetics
title Okadaic acid-dependent induction of the urokinase-type plasminogen activator gene associated with stabilization and autoregulation of c-Jun
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