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  • Title: The proto-oncogenes c-fos and c-jun modulate thyroid hormone inhibition of human thyrotropin beta subunit gene expression in opposite directions.
    Author: Bodenner DL, McClaskey JH, Kim MK, Mixson AJ, Weintraub BD.
    Journal: Biochem Biophys Res Commun; 1992 Dec 15; 189(2):1050-6. PubMed ID: 1335239.
    Abstract:
    The sequence from -1 to +6 bp in the hTSH beta 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 hTSH beta 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 hTSH beta 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.
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