ARID2 explained

AT-rich interactive domain-containing protein 2 (ARID2) is a protein that in humans is encoded by the ARID2 gene.^[1]

Function

ARID2 is a subunit of the PBAF chromatin-remodeling complex, which facilitates ligand-dependent transcriptional activation by nuclear receptors.

Structure

The ARID2 protein contains two conserved C-terminal C2H2 zinc fingers motifs, a region rich in the amino acid residues proline and glutamine, a RFX (regulatory factor X)-type winged-helix DNA-binding domain, and a conserved N-terminal AT-rich DNA interaction domain—the last domain for which the protein is named.

Clinical significance

Mutation studies have revealed ARID2 to be a significant tumor suppressor in many cancer subtypes. ARID2 mutations are prevalent in hepatocellular carcinoma^[2] and melanoma.^{[3] [4]} Mutations are present in a smaller but significant fraction in a wide range of other tumors.^[5] ARID2 mutations are enriched in hepatitis C virus-associated hepatocellular carcinoma in the US and European patient populations compared with the overall mutation frequency.^[6]

Further reading

• Martens JA, Winston F . Recent advances in understanding chromatin remodeling by Swi/Snf complexes . Current Opinion in Genetics & Development . 13 . 2 . 136–42 . Apr 2003 . 12672490 . 10.1016/S0959-437X(03)00022-4 .
• Nagase T, Kikuno R, Nakayama M, Hirosawa M, Ohara O . Prediction of the coding sequences of unidentified human genes. XVIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro . DNA Research . 7 . 4 . 273–81 . Aug 2000 . 10997877 . 10.1093/dnares/7.4.271 . free .
• Mohrmann L, Langenberg K, Krijgsveld J, Kal AJ, Heck AJ, Verrijzer CP . Differential targeting of two distinct SWI/SNF-related Drosophila chromatin-remodeling complexes . Molecular and Cellular Biology . 24 . 8 . 3077–88 . Apr 2004 . 15060132 . 381637 . 10.1128/MCB.24.8.3077-3088.2004 .
• Brandenberger R, Wei H, Zhang S, Lei S, Murage J, Fisk GJ, Li Y, Xu C, Fang R, Guegler K, Rao MS, Mandalam R, Lebkowski J, Stanton LW . Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation . Nature Biotechnology . 22 . 6 . 707–16 . Jun 2004 . 15146197 . 10.1038/nbt971 . 27764390 .
• Diederichs S, Bäumer N, Ji P, Metzelder SK, Idos GE, Cauvet T, Wang W, Möller M, Pierschalski S, Gromoll J, Schrader MG, Koeffler HP, Berdel WE, Serve H, Müller-Tidow C . Identification of interaction partners and substrates of the cyclin A1-CDK2 complex . The Journal of Biological Chemistry . 279 . 32 . 33727–41 . Aug 2004 . 15159402 . 10.1074/jbc.M401708200 . free .
• Patsialou A, Wilsker D, Moran E . DNA-binding properties of ARID family proteins . Nucleic Acids Research . 33 . 1 . 66–80 . 2005 . 15640446 . 546134 . 10.1093/nar/gki145 .
• Wilsker D, Probst L, Wain HM, Maltais L, Tucker PW, Moran E . Nomenclature of the ARID family of DNA-binding proteins . Genomics . 86 . 2 . 242–51 . Aug 2005 . 15922553 . 10.1016/j.ygeno.2005.03.013 .
• Yan Z, Cui K, Murray DM, Ling C, Xue Y, Gerstein A, Parsons R, Zhao K, Wang W . PBAF chromatin-remodeling complex requires a novel specificity subunit, BAF200, to regulate expression of selective interferon-responsive genes . Genes & Development . 19 . 14 . 1662–7 . Jul 2005 . 15985610 . 1176002 . 10.1101/gad.1323805 .
• Zhang X, Azhar G, Zhong Y, Wei JY . Zipzap/p200 is a novel zinc finger protein contributing to cardiac gene regulation . Biochemical and Biophysical Research Communications . 346 . 3 . 794–801 . Aug 2006 . 16782067 . 10.1016/j.bbrc.2006.05.211 .

Notes and References

1. Web site: Entrez Gene: ARID2 AT rich interactive domain 2 (ARID, RFX-like).
2. Li M, Zhao H, Zhang X, Wood LD, Anders RA, Choti MA, Pawlik TM, Daniel HD, Kannangai R, Offerhaus GJ, Velculescu VE, Wang L, Zhou S, Vogelstein B, Hruban RH, Papadopoulos N, Cai J, Torbenson MS, Kinzler KW . Inactivating mutations of the chromatin remodeling gene ARID2 in hepatocellular carcinoma . Nature Genetics . 43 . 9 . 828–9 . Sep 2011 . 21822264 . 3163746 . 10.1038/ng.903 .
3. Hodis E, Watson IR, Kryukov GV, Arold ST, Imielinski M, Theurillat JP, Nickerson E, Auclair D, Li L, Place C, Dicara D, Ramos AH, Lawrence MS, Cibulskis K, Sivachenko A, Voet D, Saksena G, Stransky N, Onofrio RC, Winckler W, Ardlie K, Wagle N, Wargo J, Chong K, Morton DL, Stemke-Hale K, Chen G, Noble M, Meyerson M, Ladbury JE, Davies MA, Gershenwald JE, Wagner SN, Hoon DS, Schadendorf D, Lander ES, Gabriel SB, Getz G, Garraway LA, Chin L . A landscape of driver mutations in melanoma . Cell . 150 . 2 . 251–63 . Jul 2012 . 22817889 . 3600117 . 10.1016/j.cell.2012.06.024 .
4. Krauthammer M, Kong Y, Ha BH, Evans P, Bacchiocchi A, McCusker JP, Cheng E, Davis MJ, Goh G, Choi M, Ariyan S, Narayan D, Dutton-Regester K, Capatana A, Holman EC, Bosenberg M, Sznol M, Kluger HM, Brash DE, Stern DF, Materin MA, Lo RS, Mane S, Ma S, Kidd KK, Hayward NK, Lifton RP, Schlessinger J, Boggon TJ, Halaban R . Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma . Nature Genetics . 44 . 9 . 1006–14 . Sep 2012 . 22842228 . 3432702 . 10.1038/ng.2359 .
5. Shain AH, Pollack JR . The spectrum of SWI/SNF mutations, ubiquitous in human cancers . PLOS ONE . 8 . 1 . e55119 . 2013 . 23355908 . 3552954 . 10.1371/journal.pone.0055119 . 2013PLoSO...855119S . free .
6. Zhao H, Wang J, Han Y, Huang Z, Ying J, Bi X, Zhao J, Fang Y, Zhou H, Zhou J, Li Z, Zhang Y, Yang X, Yan T, Wang L, Torbenson MS, Cai J . ARID2: a new tumor suppressor gene in hepatocellular carcinoma . Oncotarget . 2 . 11 . 886–91 . Nov 2011 . 22095441 . 3259997 . 10.18632/oncotarget.355.