PMID: 8942992Nov 26, 1996Paper

A critical arginine residue mediates cooperativity in the contact interface between transcription factors NFAT and AP-1

Proceedings of the National Academy of Sciences of the United States of America
B R PetersonG L Verdine

Abstract

The heterologous transcription factors NFAT and AP-1 coordinately regulate cytokine gene expression through cooperative binding to precisely juxtaposed DNA recognition elements. The molecular origins of cooperativity in the binding of NFAT and AP-1 to DNA are poorly understood. Herein we have used yeast one-hybrid screening and alanine-scanning mutagenesis to identify residues in AP-1 that affect cooperative interactions with NFAT on DNA. Mutation of a single conserved Arg residue to Ala in the cJun spacer region (R285A) led to a virtually complete abolition of cooperative interactions with NFAT. The DNA-binding activity of AP-1 alone was unaffected by the cJun R285A mutation, thus indicating that this residue influences cooperative binding only. Ala-scanning mutations elsewhere in AP-1, including the cFos subunit, revealed no other strongly interacting single positions. We thus conclude that NFAT contacts AP-1 in the spacer region of the cJun subunit, making an especially important contact to R285, and that these interactions drive formation of the cooperative NFAT/AP-1/DNA complex. These results provide a general strategy for selectively ablating cooperativity between transcription factors without affecting their ability to a...Continue Reading

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Citations

Oct 30, 1998·Cellular Signalling·E S MasudaN Arai
Jul 17, 1998·Current Opinion in Chemical Biology·A M Baranger
Nov 6, 2007·Molecular Biology of the Cell·Grzegorz T GurdaJohn A Williams
Mar 10, 2001·Cold Spring Harbor Symposia on Quantitative Biology·L ChenS C Harrison
Mar 16, 2006·Molecular and Cellular Biology·Sungeun KimRon Wisdom
Jul 20, 1999·Annual Review of Biophysics and Biomolecular Structure·C Wolberger
Jul 8, 1998·Proceedings of the National Academy of Sciences of the United States of America·R J DieboldT K Kerppola
May 13, 1997·Proceedings of the National Academy of Sciences of the United States of America·L J SunG L Verdine
Nov 25, 1998·Proceedings of the National Academy of Sciences of the United States of America·M ChytilG L Verdine
Sep 1, 2007·European Journal of Pharmacology·Daisaku KobayashiNorimichi Nakahata
Jun 26, 2007·Journal of Molecular Biology·Marta B WisniewskaJonathan B Weitzman
Feb 27, 1999·Current Opinion in Structural Biology·L Chen
Dec 2, 1999·Experimental Cell Research·R Wisdom
Apr 26, 2000·Chemistry & Biology·D A Erlanson
Jun 5, 2004·Journal of Molecular Biology·Marie de LumleyJonathan M Blackburn
Jul 9, 2005·Chembiochem : a European Journal of Chemical Biology·Daniel D Clark, Blake R Peterson
Sep 9, 2005·The Journal of Biological Chemistry·Sunghyun KangPatrick G Hogan
Nov 17, 2006·American Journal of Physiology. Cell Physiology·Victoria C TuQin M Chen
Jul 10, 1999·The Journal of Biological Chemistry·X M Zhang, G L Verdine
Feb 20, 1999·The Journal of Biological Chemistry·U FürstenauW Knepel
Jun 13, 2001·Oncogene·F MaciánA Rao
Apr 26, 2019·Proceedings of the National Academy of Sciences of the United States of America·Giuliana P MognolPatrick G Hogan
May 13, 2006·The Journal of General Virology·Alicia M Hidalgo-EstévezManuel Fresno
Oct 24, 2000·Biochimica Et Biophysica Acta·E SerflingA Avots
Sep 17, 2003·Genes & Development·Patrick G HoganAnjana Rao

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