Yumita Wataru, Ikeo Yasuto, Yamauchi Keishi, Sakurai Akihiro, Hashizume Kiyoshi
Department of Aging Medicine and Geriatrics, Shinshu University School of Medicine, Matsumoto, Japan.
Int J Cancer. 2003 Mar 1;103(6):738-44. doi: 10.1002/ijc.10885.
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.
据报道，MEN1基因的翻译产物——Menin蛋白，可抑制JunD介导的活化蛋白-1（AP-1）反式激活，并抑制Ras介导的肿瘤形成，但其分子机制和生理意义尚未完全阐明。为了更好地理解Menin作为肿瘤抑制因子的功能，我们研究了Menin对生理诱导的AP-1活性的影响。Menin的过表达强烈抑制了CHO-IR细胞中胰岛素诱导的AP-1活性，该细胞系高表达胰岛素受体。我们发现，Menin在转录水平上抑制c-Fos的诱导，尽管这并不能完全解释Menin抑制AP-1的机制。除了c-Fos外，Menin不改变AP-1蛋白的表达水平、c-Jun和JunD的磷酸化以及AP-1蛋白的DNA结合特性。Menin对AP-1激活的抑制可能通过两种独立机制发挥作用，即直接抑制AP-1介导的转录和抑制c-Fos的诱导。Menin抑制AP-1功能的分子机制有待进一步阐明。
