title: Correlation of transcriptional repression by p21(SNFT) with changes in DNA.NF-AT complex interactions.
abstract: p21(SNFT) (21-kDa small nuclear factor isolated from T cells) is a novel human protein of the basic leucine zipper family. The overexpression of p21(SNFT) leads to the significant and specific repression of transcription from the interleukin-2 promoter as well as from several essential activator protein 1 (AP-1)-driven composite promoter elements. One example is the distal nuclear factor of activated T cells (NF-AT)/AP-1 element where the AP-1 (Fos/Jun) basic leucine zipper heterodimer interacts with members of the NF-AT family. p21(SNFT) has been shown to replace Fos in dimerization with Jun on a consensus AP-1 binding site (12-O-tetradecanolyphorbol-13-acetate response element (TRE)) and to interact with Jun and NF-AT at the distal NF-AT/AP-1 enhancer element. A detailed biochemical analysis presented here compares interactions involving p21(SNFT) with those involving Fos. The results demonstrate that a p21(SNFT)/Jun dimer binds a TRE similarly to AP-1 and like AP-1 binds cooperatively with NF-AT at the NF-AT/AP-1 composite element. However, Fos interacts significantly more efficiently than p21(SNFT) with Jun and NF-AT, and the replacement of Fos by p21(SNFT) in the trimolecular complex drastically alters protein-DNA contacts. The data suggest that p21(SNFT) may repress transcriptional activity by inducing a unique conformation in the transcription factor complex.
authors.affiliation: Department of Biology, San Diego State University, San Diego, California 92182-4614, USA.
authors.forename: Kristen E
authors.initials: KE
authors.lastname: Bower
authors.forename: Robert W
authors.initials: RW
authors.lastname: Zeller
authors.forename: William
authors.initials: W
authors.lastname: Wachsman
authors.forename: Tara
authors.initials: T
authors.lastname: Martinez
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: McGuire
mesh_terms: D050976:Basic-Leucine Zipper Transcription Factors; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D018983:DNA Footprinting; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019281:Dimerization; D004742:Enhancer Elements, Genetic; D049452:Green Fluorescent Proteins; D006367:HeLa Cells; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics; D008164:Luminescent Proteins / Q000378:metabolism; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: C411483:BATF3 protein, human; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D007376:Interleukin-2; D008164:Luminescent Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D016755:Proto-Oncogene Proteins c-jun; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D004247:DNA