Expansion of CREB's DNA recognition specificity by Tax results from interaction with Ala-Ala-Arg at positions 282-284 near the conserved DNA- binding domain of CREB

N. Adya, L. J. Zhao, W. Huang, I. Boros, C. Z. Giam

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

The transactivator protein of human T-lymphotropic virus type I (HTLV-I), Tax, forms multiprotein complexes with the ubiquitous transcription factor CREB and the CREB/ATF-1 heterodimer. The interaction between Tax and CREB is highly specific and results in increased binding of the Tax/CREB complexes to the HTLV-I 21-bp repeats. Despite the extensive sequence similarities between CREB and ATF-1, Tax interacts with ATF-1 only marginally. Compared with CREB, Tax/CREB exhibits greatly increased DNA recognition specificity and preferentially assembles on a consensus binding site, GGGGG(T/A)TGACG(T/C)(A/C)TA(T/C)CCCCC, homologous to the HTLV-I 21-bp repeats. Here we report that Tax affects CREB binding to the Tax-inducible DNA elements by interacting with the basic-leucine zipper (bZip) domain of CREB. We show by domain switching that the basic region in CREB bZip can confer on c-Jun and ATF-1 leucine zippers the ability to interact with Tax in vitro. Mutational analyses further demonstrate that the amino acid residues of CREB critical for Tax/CREB interaction are Ala-Ala-Arg at positions 282- 284 (AAR284), immediately upstream of the highly conserved DNA-binding domain (R/K)XX(R/K)N(R/K)XAAXX(S/C)RX(R/K)(K/R) characteristic of all bZip proteins. Specific amino acid substitutions in AAR284 of CREB weakened or abolished Tax/CREB interaction, whereas reciprocal changes in ATF-1 allowed it to interact with Tax. These results support a model in which the specific interaction between Tax and the AAR284 residues near the DNA-binding domain of CREB results in a multiprotein complex with altered DNA recognition property. This protein complex assembles selectively on the viral Tax- responsive 21-bp repeats to augment transcription.

Original languageEnglish
Pages (from-to)5642-5646
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number12
DOIs
Publication statusPublished - 1994

Keywords

  • cAMP response element
  • human T-lymphotropic virus type I
  • leucine zipper
  • protein-protein interaction

ASJC Scopus subject areas

  • General

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