原癌基因c-fos和c-jun以相反的方向调节甲状腺激素对人促甲状腺素β亚基基因表达的抑制作用。

The proto-oncogenes c-fos and c-jun modulate thyroid hormone inhibition of human thyrotropin beta subunit gene expression in opposite directions.

作者信息

Bodenner D L, McClaskey J H, Kim M K, Mixson A J, Weintraub B D

机构信息

Molecular and Cellular Endocrinology Branch (MCEB), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.

出版信息

Biochem Biophys Res Commun. 1992 Dec 15;189(2):1050-6. doi: 10.1016/0006-291x(92)92310-t.

DOI:10.1016/0006-291x(92)92310-t

PMID: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.

摘要

人促甲状腺激素β基因中从 -1 到 +6 碱基对的序列包含重叠的假定甲状腺激素反应元件和 AP-1 反应元件。我们通过使用 -125 到 +37 碱基对的人促甲状腺激素β片段进行瞬时转染实验，证明了该区域中 AP-1 成分 c-fos 和 c-jun 与甲状腺激素受体之间的相互作用。c-jun 完全消除了 T3 抑制作用，但 c-fos 使其增加了三倍。在 +2 碱基对处的单个颠换突变在存在 c-jun 的情况下恢复了 T3 抑制作用，并通过凝胶迁移率变动分析显著降低了纯化的 c-jun 的结合。因此，c-fos 和 c-jun 通过与甲状腺激素受体共享的反应元件以相反方向影响 T3 对人促甲状腺激素β表达的抑制作用。控制这两个原癌基因的相对细胞水平可能在调节甲状腺激素抑制反应中起主要作用。