Modulation of cellular AP-1 DNA binding activity by heat shock proteins

Abstract

Recent studies have indicated that ubiquitously expressed molecular chaperones of the heat shock protein (Hsp) class may have an additional, nuclear, role in the regulation of gene expression. Experiments on cellular transcription factors derived from the rat adrenal gland have now shown that Hsps modulate in vitro DNA binding activity of the AP-1 factor. Both Hsc70 (p73) and Hsp70 (p72) were demonstrated to exert this effect through a mechanism that appears to be independent of both redox, and phosphorylation state. Further studies on the effect of Hsps on recombinant Fos/Jun protein binding activity indicated that the mechanism of action involves a selective attenuation of high affinity c-Fos:c-Jun binding as compared with c-Jun homodimer binding activity. Because cellular and physiological stress are associated with the induction of both AP-1 and Hsps it is apparent that Hsps may play a modulatory role in the regulation of AP-1 responsive genes.