Yang Ying, Cvekl Ales
Departments of Ophthalmology and Visual Sciences and Molecular Genetics, Albert Einstein College of Medicine, Bronx, New York 10461.
Einstein J Biol Med. 2007;23(1):2-11. doi: 10.23861/ejbm20072347.
A large number of mammalian transcription factors possess the evolutionary conserved basic and leucine zipper domain (bZIP). The basic domain interacts with DNA while the leucine zipper facilitates homo- and hetero-dimerization. These factors can be grouped into at least seven families: AP-1, ATF/CREB, CNC, C/EBP, Maf, PAR, and virus-encoded bZIPs. Here, we focus on a group of four large Maf proteins: MafA, MafB, c-Maf, and NRL. They act as key regulators of terminal differentiation in many tissues such as bone, brain, kidney, lens, pancreas, and retina, as well as in blood. The DNA-binding mechanism of large Mafs involves cooperation between the basic domain and an adjacent ancillary DNA-binding domain. Many genes regulated by Mafs during cellular differentiation use functional interactions between the Pax/Maf, Sox/Maf, and Ets/Maf promoter and enhancer modules. The prime examples are crystallin genes in lens and glucagon and insulin in pancreas. Novel roles for large Mafs emerged from studying generations of MafA and MafB knockouts and analysis of combined phenotypes in double or triple null mice. In addition, studies of this group of factors in invertebrates revealed the evolutionarily conserved function of these genes in the development of multicellular organisms.
大量哺乳动物转录因子拥有进化保守的碱性亮氨酸拉链结构域（bZIP）。碱性结构域与DNA相互作用，而亮氨酸拉链则促进同源和异源二聚化。这些因子可至少分为七个家族：AP-1、ATF/CREB、CNC、C/EBP、Maf、PAR和病毒编码的bZIP。在此，我们聚焦于一组四种大型Maf蛋白：MafA、MafB、c-Maf和NRL。它们在许多组织（如骨骼、大脑、肾脏、晶状体、胰腺和视网膜）以及血液中作为终末分化的关键调节因子发挥作用。大型Maf的DNA结合机制涉及碱性结构域与相邻辅助DNA结合结构域之间的协作。Maf在细胞分化过程中调控的许多基因利用Pax/Maf、Sox/Maf和Ets/Maf启动子及增强子模块之间的功能相互作用。主要例子是晶状体中的晶体蛋白基因以及胰腺中的胰高血糖素和胰岛素基因。对MafA和MafB基因敲除世代的研究以及对双敲除或三敲除小鼠联合表型的分析揭示了大型Maf的新作用。此外，对无脊椎动物中这组因子的研究揭示了这些基因在多细胞生物发育中的进化保守功能。
