Suppression of insulin-induced AP-1 transactivation by menin accompanies inhibition of c-Fos induction.
The translation product of the MEN1 gene, menin, has been reported to suppress JunD-mediated activator protein-1 (AP-1) transactivation and inhibit Ras-mediated tumor formation, but its molecular mechanisms and physiologic significance have been poorly elucidated. To better understand the function of menin as a tumor suppressor, we examined the effect of menin on physiologically induced AP-1 activity. Overexpression of menin strongly suppressed insulin-induced AP-1 activity in CHO-IR cells, which express high levels of insulin receptor. We found that menin suppressed c-Fos induction at the transcriptional level, although that cannot explain the entire mechanism of AP-1 suppression by menin. Menin did not alter the expression levels of AP-1 proteins except c-Fos, phosphorylation of c-Jun and JunD and DNA binding properties of AP-1 proteins. Suppression of AP-1 activation by menin may be exerted through 2 independent mechanisms, direct inhibition on AP-1-mediated transcription and suppression of c-Fos induction. The molecular mechanism of inhibition of AP-1 function by menin needs further elucidation.
Yumita
Wataru
W
Department of Aging Medicine and Geriatrics, Shinshu University School of Medicine, Matsumoto, Japan.
Ikeo
Yasuto
Y
Yamauchi
Keishi
K
Sakurai
Akihiro
A
Hashizume
Kiyoshi
K
D000818:Animals; D001665:Binding Sites; D015152:Blotting, Northern; D015153:Blotting, Western; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D015536:Down-Regulation; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015151:Immunoblotting; D007328:Insulin / Q000494:pharmacology*; D008156:Luciferases / Q000378:metabolism; D046911:Macromolecular Substances; D009363:Neoplasm Proteins / Q000494:pharmacology*; D010766:Phosphorylation; D010957:Plasmids; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects*
D007328:Insulin; C105373:MEN1 protein, human; D046911:Macromolecular Substances; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D008156:Luciferases