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Suppression of AP-1 activity by cycloprodigiosin hydrochloride.

Abstract
Cycloprodigiosin hydrochloride (cPrG.HCl), a compound isolated from a marine bacterium, acts as an immunosuppressant and an anti-cancer drug. We have previously reported that cPrG.HCl suppressed the transcriptional activation of nuclear factor (NF)-kappaB. Here we studied the effect of cPrG.HCl on activation of another transcription factor, activator protein 1 (AP-1). cPrG.HCl potently suppressed AP-1 activity induced by tumor necrosis factor (TNF) alpha and phorbol myristate acetate (PMA). cPrG.HCl did not inhibit any of the mitogen-activated protein kinase (MAPK) families, whereas it did suppress transcriptional activation of AP-1 induced by constitutively activated mutants of MEKK1 or Ras. cPrG.HCl inhibited neither TNFalpha- or PMA-induced DNA-binding of AP-1 nor co-activator p300-induced activation of AP-1. Taken together, cPrG.HCl suppresses AP-1-dependent gene expression downstream of MAPK group through the inhibition of the transcription activation step of the AP-1 promoter complex.
AuthorsKeiko Kawauchi, Kei Tobiume, Shuhei Kaneko, Keiko Kaneshiro, Shiho Okamoto, Emi Ueda, Hideaki Kamata, Yoshinori Moriyama, Hajime Hirata
JournalBiological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 30 Issue 9 Pg. 1792-5 (Sep 2007) ISSN: 0918-6158 [Print] Japan
PMID17827742 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Immunosuppressive Agents
  • Indoles
  • NF-kappa B
  • Pyrroles
  • Transcription Factor AP-1
  • Tumor Necrosis Factor-alpha
  • cycloprodigiosin
  • Luciferases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • Tetradecanoylphorbol Acetate
Topics
  • Biotransformation (drug effects)
  • Blotting, Western
  • Cell Line, Tumor
  • Electrophoretic Mobility Shift Assay
  • Genes, Reporter (genetics)
  • HeLa Cells
  • Humans
  • Immunosuppressive Agents (pharmacology)
  • Indoles (pharmacology)
  • JNK Mitogen-Activated Protein Kinases (metabolism)
  • Luciferases (genetics)
  • Mitogen-Activated Protein Kinase 3 (metabolism)
  • Mitogen-Activated Protein Kinases (metabolism)
  • NF-kappa B (genetics)
  • Plasmids (genetics)
  • Pyrroles (pharmacology)
  • Tetradecanoylphorbol Acetate (pharmacology)
  • Transcription Factor AP-1 (antagonists & inhibitors)
  • Tumor Necrosis Factor-alpha (pharmacology)

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