Correlation of transcriptional repression by p21SNFT with changes in DNA·NF-AT complex interactions

Abstract

p21SNFT (21-kDa small nuclear factor isolated from T cells) is a novel human protein of the basic leucine zipper family. The overexpression of p21SNFT 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. p21SNFT has been shown to replace Fos in dimerization with Jun on a consensus AP-1 binding site (12-O-tetradecanolyphor. bol-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 p21SNFT with those involving Fos. The results demonstrate that a p21SNFT/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 p21SNFT with Jun and NF-AT, and the replacement of Fos by p21SNFT in the trimolecular complex drastically alters protein-DNA contacts. The data suggest that p21SNFT may repress transcriptional activity by inducing a unique conformation in the transcription factor complex.