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

被引:5
作者
BODENNER, DL
MCCLASKEY, JH
KIM, MK
MIXSON, AJ
WEINTRAUB, BD
机构
[1] Molecular and Cellular Endocrinology Branch (MCEB), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda
关键词
D O I
10.1016/0006-291X(92)92310-T
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1050 / 1056
页数:7
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