Suppression of AP-1 activity by cycloprodigiosin hydrochloride.
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.
Kawauchi
Keiko
K
Department of Molecular Oncology, Institute of Gerontology, Nippon Medical School, Kanagawa 211-8533, Japan. kawauchi@nms.ac.jp
Tobiume
Kei
K
Kaneko
Shuhei
S
Kaneshiro
Keiko
K
Okamoto
Shiho
S
Ueda
Emi
E
Kamata
Hideaki
H
Moriyama
Yoshinori
Y
Hirata
Hajime
H
D001711:Biotransformation / Q000187:drug effects; D015153:Blotting, Western; D045744:Cell Line, Tumor; D024202:Electrophoretic Mobility Shift Assay; D017930:Genes, Reporter / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008156:Luciferases / Q000235:genetics; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D011758:Pyrroles / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology