THE COMPETITIVE-BINDING OF STAT3 AND NF-KAPPA-B ON AN OVERLAPPING DNA-BINDING SITE

Interleukin-1 (IL-1) and interleukin-6 (IL-6), two early-response cyto kines expressed during an acute inflammatory reaction, regulate the ex pression of several acute phase proteins (APP) in the liver. IL-1 rela ys its signal to specific genes via NF-kappa B, whereas IL-6 sends its signal to the nucleus via STAT1 alpha and STAT3. Interestingly, overl apping binding sites for STAT3 and NF-kappa B can be found on promoter s of several APP genes. We show here that both STAT3 and NF-kappa B ar e active during inflammation and are capable of binding to a STAT3/NF- kappa B overlapping DNA motif derived from the alpha(2)-macroglobulin gene promoter. In vitro binding assays demonstrated that NF-kappa B co mpetes with STAT3 binding on this probe. Our results suggest that thes e transcription factors regulate each others' function through competi tion for overlapping DNA binding sites. (C) 1997 Academic Press.