THE PROTOONCOGENES C-FOS AND C-JUN MODULATE THYROID-HORMONE INHIBITION OF HUMAN THYROTROPIN-BETA SUBUNIT GENE-EXPRESSION IN OPPOSITE DIRECTIONS

The sequence from -1 to +6 bp in the hTSHβ gene contains overlapping putative thyroid hormone and AP-1 response elements. We demonstrate interaction between the AP-1 constituents c-fos and c-jun and thyroid hormone receptor in this region by transient transfection experiments using a -125 to +37 bp hTSHβ fragment. T3 inhibition was completely abolished by c-jun, but increased threefold by c-fos. A single transversion mutation at +2 bp restored T3 inhibition in the presence of c-jun and markedly reduced binding of purified c-jun by gel mobility shift assay. Thus, c-fos and c-jun influence T3 inhibition of hTSHβ expression in opposite directions acting through a response element shared with thyroid hormone receptor. Control of the relative cellular levels of these two proto-oncogenes may play a major role in modulating thyroid hormone inhibitory responses. © 1992.