Wilsker Deborah, Patsialou Antonia, Dallas Peter B, Moran Elizabeth
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Cell Growth Differ. 2002 Mar;13(3):95-106.
The ARID family of DNA binding proteins was first recognized approximately 5 years ago. The founding members, murine Bright and Drosophila dead ringer (Dri), were independently cloned on the basis of their ability to bind to AT-rich DNA sequences, although neither cDNA encoded a recognizable DNA binding domain. Mapping of the respective binding activities revealed a shared but previously unrecognized DNA binding domain, the consensus sequence of which extends across approximately 100 amino acids. This novel DNA binding domain was designated AT-rich interactive domain (ARID), based on the behavior of Bright and Dri. The consensus sequence occurs in 13 distinct human proteins and in proteins from all sequenced eukaryotic organisms. The majority of ARID-containing proteins were not cloned in the context of DNA binding activity, however, and their features as DNA binding proteins are only beginning to be investigated. The ARID region itself shows more diversity in structure and function than the highly conserved consensus sequence suggests. The basic structure appears to be a series of six alpha-helices separated by beta-strands, loops, or turns, but the structured region may extend to an additional helix at either or both ends of the basic six. It has also become apparent that the DNA binding activity of ARID-containing proteins is not necessarily sequence specific. What is consistent is the evidence that family members play vital roles in the regulation of development and/or tissue-specific gene expression. Inappropriate expression of ARID proteins is also increasingly implicated in human tumorigenesis. This review summarizes current knowledge about the structure and function of ARID family members, with a particular focus on the human proteins.
DNA结合蛋白的ARID家族大约在5年前首次被识别。该家族的创始成员，小鼠的Bright和果蝇的死环蛋白（Dri），是基于它们与富含AT的DNA序列结合的能力而被独立克隆出来的，尽管这两个cDNA都没有编码一个可识别的DNA结合结构域。对各自结合活性的定位揭示了一个共享但此前未被识别的DNA结合结构域，其共有序列延伸约100个氨基酸。基于Bright和Dri的行为，这个新的DNA结合结构域被命名为富含AT的相互作用结构域（ARID）。该共有序列存在于13种不同的人类蛋白质以及所有已测序真核生物的蛋白质中。然而，大多数含有ARID的蛋白质并不是在DNA结合活性的背景下被克隆的，它们作为DNA结合蛋白的特性才刚刚开始被研究。ARID区域本身在结构和功能上表现出的多样性比高度保守的共有序列所显示的要多。其基本结构似乎是由β链、环或转角分隔的一系列六个α螺旋，但结构区域可能会在基本的六个螺旋的一端或两端延伸至另外一个螺旋。同样明显的是，含有ARID的蛋白质的DNA结合活性不一定具有序列特异性。一致的证据是，该家族成员在发育调控和/或组织特异性基因表达中发挥着至关重要的作用。ARID蛋白的不适当表达也越来越多地与人类肿瘤发生有关。本综述总结了关于ARID家族成员结构和功能的当前知识，特别关注人类蛋白质。
