Department of Biology, McMaster University, Hamilton, Ontario, Canada.
Adv Exp Med Biol. 2009;668:27-36. doi: 10.1007/978-1-4419-1664-8_3.
The cloning of the MEN1 gene in 1997 led to the characterization of menin, the protein behind the multiple endocrine neoplasia Type 1 syndrome. Menin, a novel nuclear protein with no homology to other gene products, is expressed ubiquitously. MEN1 missense mutations are dispersed along the coding region of the gene but are more common in the most conserved regions. Likewise, domains of protein interaction often correspond to the more conserved segments of menin. These protein interactions are generally facilitated by multiple domains or encompass a large portion of menin. The exception to this rule is a small stretch of amino acids mediating the interaction of menin with the mSin3A corepressor and histone deacetylase complexes. The C-terminal region of menin harbors several nuclear localization signals that play redundant functions in the localization of menin to the nuclear compartment. The nuclear localization signals are also important for the interaction of menin with the nuclear matrix. Menin is the target of several kinases and a candidate substrate of the ATM/ATR kinases, implying a role for this tumor suppressor in the DNA damage response. Menin is highly conserved from Drosophila to human but is absent in the nematode and in yeast.
1997 年 MEN1 基因的克隆导致了 menin 的特征描述，这是多发性内分泌肿瘤 1 型综合征背后的蛋白质。Menin 是一种新型核蛋白，与其他基因产物没有同源性，广泛表达。MEN1 错义突变散布在基因的编码区，但在更保守的区域更为常见。同样，蛋白相互作用的结构域通常与 menin 更保守的片段相对应。这些蛋白相互作用通常由多个结构域促进，或者包含 menin 的很大一部分。这个规则的例外是一小段氨基酸介导 menin 与 mSin3A 核心抑制因子和组蛋白去乙酰化酶复合物的相互作用。Menin 的 C 末端区域含有几个核定位信号，这些信号在将 menin 定位到核区室中具有冗余功能。核定位信号对于 menin 与核基质的相互作用也很重要。Menin 是几种激酶的靶标，也是 ATM/ATR 激酶的候选底物，这意味着该肿瘤抑制因子在 DNA 损伤反应中具有重要作用。Menin 从果蝇到人类都高度保守，但在线虫和酵母中不存在。
