The proto-oncogenes 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 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.
Bodenner
D L
DL
Molecular and Cellular Endocrinology Branch (MCEB), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
McClaskey
J H
JH
Kim
M K
MK
Mixson
A J
AJ
Weintraub
B D
BD
D001483:Base Sequence; D002460:Cell Line; D004247:DNA / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos; D016758:Genes, jun; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010920:Placenta; D010957:Plasmids; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D011519:Proto-Oncogenes; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism; D013972:Thyrotropin / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D014284:Triiodothyronine / Q000494:pharmacology*
D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D013972:Thyrotropin; D004247:DNA