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Cell Growth & Differentiation Vol. 13, 95-106, March 2002
© 2002 American Association for Cancer Research

Review

ARID Proteins

A Diverse Family of DNA Binding Proteins Implicated in the Control of Cell Growth, Differentiation, and Development1

Deborah Wilsker, Antonia Patsialou, Peter B. Dallas and Elizabeth Moran2

Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140 [D. W., A. P., E. M.], and TVW Telethon Institute for Child Health Research and the Center for Child Health Research, University of Western Australia, Subiaco, Western Australia 6008 [P. B. D.]

The ARID family of DNA binding proteins was first recognized ~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 ~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 ß-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.




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