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Suppression of insulin‐induced AP‐1 transactivation by menin accompanies inhibition of c‐Fos induction
Author(s) -
Yumita Wataru,
Ikeo Yasuto,
Yamauchi Keishi,
Sakurai Akihiro,
Hashizume Kiyoshi
Publication year - 2002
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.10885
Subject(s) - transactivation , men1 , activator (genetics) , transcription factor , suppressor , chemistry , transcription (linguistics) , phosphorylation , cancer research , biology , microbiology and biotechnology , receptor , gene , biochemistry , linguistics , philosophy , multiple endocrine neoplasia
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.