PMID- 8202541 OWN - NLM STAT- MEDLINE DCOM- 19940706 LR - 20190501 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 91 IP - 12 DP - 1994 Jun 7 TI - 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. PG - 5642-6 AB - 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)C-CCCC, 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. FAU - Adya, N AU - Adya N AD - Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4984. FAU - Zhao, L J AU - Zhao LJ FAU - Huang, W AU - Huang W FAU - Boros, I AU - Boros I FAU - Giam, C Z AU - Giam CZ LA - eng GR - R01 CA48709/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Activating Transcription Factor 1) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (DNA-Binding Proteins) RN - 0 (Gene Products, tax) RN - 0 (Transcription Factors) SB - IM MH - Activating Transcription Factor 1 MH - Amino Acid Sequence MH - Base Sequence MH - Binding Sites MH - Consensus Sequence MH - Cyclic AMP Response Element-Binding Protein/*chemistry/metabolism MH - DNA-Binding Proteins/chemistry/metabolism MH - Gene Products, tax/*chemistry/metabolism MH - Human T-lymphotropic virus 1/genetics MH - Humans MH - In Vitro Techniques MH - Leucine Zippers MH - Molecular Sequence Data MH - Protein Binding MH - Transcription Factors/metabolism PMC - PMC44052 EDAT- 1994/06/07 00:00 MHDA- 1994/06/07 00:01 PMCR- 1994/12/07 CRDT- 1994/06/07 00:00 PHST- 1994/06/07 00:00 [pubmed] PHST- 1994/06/07 00:01 [medline] PHST- 1994/06/07 00:00 [entrez] PHST- 1994/12/07 00:00 [pmc-release] AID - 10.1073/pnas.91.12.5642 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5642-6. doi: 10.1073/pnas.91.12.5642.