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. © 2002 Wiley-Liss, Inc.