JunD-menin interaction regulates c-Jun-mediated AP-1 transactivation.
The gene responsible for multiple endocrine neoplasia type 1, MEN1, encodes the 610-amino acid-protein, menin. Although menin has been reported to bind AP-1 transcription factor JunD and suppress its transcriptional activity, little is known about its molecular mechanisms and physiological role. To better understand the function of menin and its significance in tumorigenesis, we investigated the effect of wild-type and mutant menin proteins on AP-1 transactivation. In COS cells, wild-type menin suppressed JunD-mediated transactivation in a dose-dependent manner, while it augmented c-Jun-mediated transactivation also in a dose-dependent manner. These effects were lost or reduced in all menin mutants examined. Electrophoretic mobility shift assay using AP-1 binding elements as a probe revealed that menin does not affect binding of c-Jun to DNA. Coexpression of menin mutants did not affect the function of wild-type menin. Coexpression of JunD amino-terminal fragment abolished menin-mediated enhancement of c-Jun transactivation, suggesting that Menin-JunD interaction may negatively regulate the enhancing effect of menin on c-Jun-mediated transactivation in COS cells.
Ikeo
Yasuto
Y
Department of Aging Medicine and Geriatrics, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
Yumita
Wataru
W
Sakurai
Akihiro
A
Hashizume
Kiyoshi
K
D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D002522:Chlorocebus aethiops; D004247:DNA / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D051379:Mice; D018761:Multiple Endocrine Neoplasia Type 1; D009154:Mutation; D010446:Peptide Fragments / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins; D018808:Transcription Factor AP-1 / Q000502:physiology*; D015533:Transcriptional Activation; D014162:Transfection
C105373:MEN1 protein, human; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; D016755:Proto-Oncogene Proteins c-jun; D011993:Recombinant Fusion Proteins; D018808:Transcription Factor AP-1; D004247:DNA