Guru S C, Prasad N B, Shin E J, Hemavathy K, Lu J, Ip Y T, Agarwal S K, Marx S J, Spiegel A M, Collins F S, Oliver B, Chandrasekharappa S C
Genetics and Molecular Biology Branch, National Human Genome Research Institute, 49 Convent Drive, Bethesda, MD 20892, USA.
Gene. 2001 Jan 24;263(1-2):31-8. doi: 10.1016/s0378-1119(00)00562-x.
Multiple endocrine neoplasia type 1 (MEN1) is a familial cancer syndrome characterized by tumors of the parathyroid, entero-pancreatic neuroendocrine and pituitary tissues and caused by inactivating mutations in the MEN1 gene. Menin, the 610-amino acid nuclear protein encoded by MEN1, binds to the transcription factor JunD and can repress JunD-induced transcription. We report here the identification of a MEN1 ortholog in Drosophila melanogaster, Menin1, that encodes a 763 amino acid protein sharing 46% identity with human menin. Additionally, 69% of the missense mutations and in-frame deletions reported in MEN1 patients appear in amino acid residues that are identical in the Drosophila and human protein, suggesting the importance of the conserved regions. Drosophila Menin1 gene transcripts use alternative polyadenylation sites resulting in 4.3 and 5-kb messages. The 4.3-kb transcript appears to be largely maternal, while the 5-kb transcript appears mainly zygotic. The binding of Drosophila menin to human JunD or Drosophila Jun could not be demonstrated by the yeast two-hybrid analysis. The identification of the MEN1 ortholog from Drosophila melanogaster will provide an opportunity to utilize Drosophila genetics to enhance our understanding of the function of human menin.
多发性内分泌腺瘤1型（MEN1）是一种家族性癌症综合征，其特征为甲状旁腺、肠-胰腺神经内分泌和垂体组织发生肿瘤，由MEN1基因的失活突变引起。Menin是由MEN1编码的610个氨基酸的核蛋白，它与转录因子JunD结合，并可抑制JunD诱导的转录。我们在此报告在黑腹果蝇中鉴定出一种MEN1直系同源物Menin1，它编码一种763个氨基酸的蛋白质，与人类Menin的同源性为46%。此外，MEN1患者中报告的69%的错义突变和框内缺失出现在果蝇和人类蛋白质中相同的氨基酸残基上，这表明保守区域的重要性。果蝇Menin1基因转录本使用不同的聚腺苷酸化位点，产生4.3 kb和5 kb的信使RNA。4.3 kb的转录本似乎主要是母源性的，而5 kb的转录本似乎主要是合子性的。酵母双杂交分析未能证明果蝇Menin与人类JunD或果蝇Jun的结合。从黑腹果蝇中鉴定出MEN1直系同源物将为利用果蝇遗传学增进我们对人类Menin功能的理解提供机会。
