Calcium Research Laboratory, Rm. H4.67, Royal Victoria Hospital, 687 Pine Avenue West, Montreal, QC H3A 1A1, Canada.
Adv Exp Med Biol. 2009;668:37-50. doi: 10.1007/978-1-4419-1664-8_4.
Since its discovery as a novel protein some 10 years ago, many cellular functions of menin have been identified. However, which ones of these relate specifically to menin's role as a tumor suppressor and which ones not remains unclear. Menin is predominantly nuclear and acts as a scaffold protein to regulate gene transcription by coordinating chromatin remodeling. It is implicated in both histone deacetylase and histone methyltransferase activity and, via the latter, regulates the expression of cell cycle kinase inhibitor and homeobox domain genes. TGF-beta family members are key cytostatic molecules and menin is a facilitator of the transcriptional activity of their signaling molecules, the Smads, thereby ensuring appropriate control of cell proliferation and differentiation.
自 10 年前发现这种新型蛋白以来,人们已经鉴定出了多种 Menin 的细胞功能。然而,哪些功能与 Menin 作为肿瘤抑制因子的作用有关,哪些无关仍不清楚。Menin 主要存在于细胞核内,作为支架蛋白通过协调染色质重塑来调节基因转录。它涉及组蛋白去乙酰化酶和组蛋白甲基转移酶的活性,并通过后者调节细胞周期激酶抑制剂和同源盒结构域基因的表达。TGF-β 家族成员是关键的细胞静止分子,Menin 是它们信号分子 Smads 转录活性的促进剂,从而确保对细胞增殖和分化的适当控制。