Large Maf Transcription Factors: Cousins of AP-1 Proteins and Important Regulators of Cellular Differentiation.
Large Maf Transcription Factors: Cousins of AP-1 Proteins and Important Regulators of Cellular Differentiation.
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DOI：
10.23861/ejbm20072347
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发表时间：
2016-03
期刊：
影响因子：
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通讯作者：
Ying Yang;A. Cvekl
中科院分区：
文献类型：
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作者：
Ying Yang;A. Cvekl
大量哺乳动物转录因子具有进化保守的碱性和亮氨酸拉链结构域（bZIP）。基本结构域与DNA相互作用，而亮氨酸拉链促进同源和异二聚化。这些因子可分为至少7个家族：AP-1、ATF/CREB、CNC、C/EBP、Maf、PAR和病毒编码的bzip。在这里，我们关注的是一组四种大型Maf蛋白：MafA、MafB、c-Maf和NRL。它们在许多组织如骨、脑、肾、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。大型maf的dna结合机制涉及基本结构域和邻近的辅助dna结合结构域之间的合作。在细胞分化过程中，许多受Maf调控的基因使用Pax/Maf、Sox/Maf和Ets/Maf启动子和增强子模块之间的功能相互作用。主要的例子是晶状体中的结晶蛋白基因、胰腺中的胰高血糖素和胰岛素。通过研究MafA和MafB基因敲除的世代以及分析双或三阴性小鼠的联合表型，大型maf的新作用出现了。此外，在无脊椎动物中对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。
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.