Shore P, Sharrocks A D
Department of Biochemistry and Genetics, Medical School, University of Newcastle upon Tyne, England.
Eur J Biochem. 1995 Apr 1;229(1):1-13. doi: 10.1111/j.1432-1033.1995.tb20430.x.
The MADS-box family of transcription factors has been defined on the basis of primary sequence similarity amongst numerous proteins from a diverse range of eukaryotic organisms including yeasts, plants, insects, amphibians and mammals. The MADS-box is a conserved motif found within the DNA-binding domains of these proteins and the name refers to four of the originally identified members: MCM1, AG, DEFA and SRF. Several proteins within this family have significant biological roles. For example, the human serum-response factor (SRF) is involved in co-ordinating transcription of the protooncogene c-fos, whilst MCM1 is central to the transcriptional control of cell-type specific genes and the pheromone response in the yeast Saccharomyces cerevisiae. The RSRF/MEF2 proteins comprise a sub-family of this class of transcription factors which are key components in muscle-specific gene regulation. Moreover, in plants, MADS-box proteins such as AG, DEFA and GLO play fundamental roles during flower development. The MADS-box is a contiguous conserved sequence of 56 amino acids, of which 9 are identical in all family members described so far. Several members have been shown to form dimers and consequently two functional regions within the MADS-box have been defined. The N-terminal half is the major determinant of DNA-binding specificity whilst the C-terminal half is necessary for dimerisation. This organisation allows the potential formation of numerous proteins, with subtly different DNA-binding specificities, from a limited number of genes by heterodimerisation between different MADS-box proteins. The majority of MADS-box proteins bind similar sites based on the consensus sequence CC(A/T)6GG although each protein apparently possesses a distinct binding specificity. Moreover, several MADS-box proteins specifically recruit other transcription factors into multi-component regulatory complexes. Such interactions with other proteins appears to be a common theme within this family and play a pivotal role in the regulation of target genes.
转录因子的MADS盒家族是根据来自多种真核生物（包括酵母、植物、昆虫、两栖动物和哺乳动物）的众多蛋白质之间的一级序列相似性来定义的。MADS盒是在这些蛋白质的DNA结合结构域中发现的一个保守基序，该名称指的是最初鉴定的四个成员：MCM1、AG、DEFA和SRF。这个家族中的几种蛋白质具有重要的生物学作用。例如，人类血清反应因子（SRF）参与原癌基因c-fos的转录协调，而MCM1对于酵母酿酒酵母中细胞类型特异性基因的转录控制和信息素反应至关重要。RSRF/MEF2蛋白构成了这类转录因子的一个亚家族，它们是肌肉特异性基因调控的关键成分。此外，在植物中，AG、DEFA和GLO等MADS盒蛋白在花发育过程中发挥着重要作用。MADS盒是一个由56个氨基酸组成的连续保守序列，到目前为止，在所有描述的家族成员中，有9个氨基酸是相同的。已证明几个成员能形成二聚体，因此在MADS盒内定义了两个功能区域。N端的一半是DNA结合特异性的主要决定因素，而C端的一半是二聚化所必需的。这种结构使得通过不同MADS盒蛋白之间的异源二聚化，能够从有限数量的基因中潜在地形成大量具有细微不同DNA结合特异性的蛋白质。大多数MADS盒蛋白基于共有序列CC(A/T)6GG结合相似的位点，尽管每种蛋白显然都具有独特的结合特异性。此外，几种MADS盒蛋白特异性地将其他转录因子招募到多组分调节复合物中。与其他蛋白质的这种相互作用似乎是这个家族中的一个共同主题，并且在靶基因的调控中起关键作用。
