Menin, the product of the MEN1 gene, is a nuclear protein
Menin, the product of the MEN1 gene, is a nuclear protein
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DOI：
10.1073/pnas.95.4.1630
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发表时间：
1998-02-17
影响因子：
11.1
通讯作者：
Chandrasekharappa, SC
中科院分区：
文献类型：
--
作者：
Guru, SC;Goldsmith, PK;Chandrasekharappa, SC
MEN 1基因，其中的突变负责多发性内分泌瘤1型（MEN 1），编码610个氨基酸的蛋白质，表示为menin。这种假定的肿瘤抑制因子的氨基酸序列没有提供蛋白质的功能或亚细胞位置的线索。我们在此报告，基于免疫荧光，Western印迹的亚细胞组分，和增强的绿色荧光蛋白的表位标记，menin主要位于细胞核中。增强的绿色荧光蛋白标记的menin缺失构建体鉴定至少两个独立的核定位信号（NLS），两者都位于蛋白质的C-末端第四位。在68个已知的独立的疾病相关突变中，22个错义和3个框内缺失都不影响任何一个推定的NLS序列。然而，如果表达，则由43个已知的移码/无义突变产生的截短的menin蛋白中没有一个将保留两个NLS。menin在细胞核中的确切作用仍有待了解。
The MEN1 gene, mutations in which are responsible for multiple endocrine neoplasia type 1 (MEN1), encodes a 610-amino acid protein, denoted menin. The amino acid sequence of this putative tumor suppressor offers no clue to the function or subcellular location of the protein. We report herein, based on immunofluorescence, Western blotting of subcellular fractions, and epitope tagging with enhanced green fluorescent protein, that menin is located primarily in the nucleus. Enhanced green fluorescent protein-tagged menin deletion constructs identify at least two independent nuclear localization signals (NLS), both located in the C-terminal fourth of the protein. Among the 68 known independent disease-associated mutations, none of the 22 missense and 3 in-frame deletions affect either of the putative NLS sequences. However, if expressed, none of the truncated menin proteins resulting from the 43 known frameshift/nonsense mutations would retain both the NLSs. The precise role(s) of menin in the nucleus remain to be understood.