Heparin decreases activator protein-1 binding to DNA in part by posttranslational modification of Jun B.
Heparin is a potent inhibitor of the proliferation and migration of vascular smooth muscle cells. This agent selectively inhibits the transcription of tissue-type plasminogen activator and interstitial collagenase, probably by decreasing the binding of activator protein-1 (AP-1) to phorbol ester-responsive elements in the promoters of these genes. Decreased AP-1 binding is not due to a direct inhibition by heparin, since heparinase digestion of nuclear extracts prepared from heparin-treated smooth muscle cells does not restore AP-1 binding activity. Treatment of cells with heparin suppresses the expression of Jun B, one of the components of AP-1. The major effect of heparin is at the level of posttranslational modification of Jun B. Results from pulse-chase labeling experiments show that the newly synthesized Jun B is rapidly converted to a higher-molecular-weight form and that conversion is suppressed by heparin. Evidence is presented suggesting that the heparin-inhibited event is phosphorylation of Jun B.
Department of Surgery, University of Washington, Seattle 98195.
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Dobrowolska
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Morris
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Clowes
D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006493:Heparin / Q000494:pharmacology*; D019763:Heparin Lyase; D018398:Homeodomain Proteins; D015778:Minor Histocompatibility Antigens; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D010215:Papio; D010766:Phosphorylation; D011133:Polysaccharide-Lyases / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051818:Replication Protein C; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
C096816:BCL2-related protein A1; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C096063:MATA1 protein, S cerevisiae; D015778:Minor Histocompatibility Antigens; D015335:Molecular Probes; D019253:Proto-Oncogene Proteins c-bcl-2; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D006493:Heparin; D004247:DNA; D051818:Replication Protein C; D011133:Polysaccharide-Lyases; D019763:Heparin Lyase; D013755:Tetradecanoylphorbol Acetate