Regulation of thyroid hormone receptor-mediated transcription by a cytosol protein.
Regulation of thyroid hormone receptor-mediated transcription by a cytosol protein.
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通过胞质蛋白调节甲状腺激素受体介导的转录。
DOI：
10.1073/pnas.89.19.9277
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发表时间：
1992
影响因子：
11.1
通讯作者：
S. Cheng
中科院分区：
文献类型：
--
作者：
K. Ashizawa;S. Cheng
甲状腺激素受体(TRs)是类固醇激素/维甲酸受体超家族的成员，调节体内平衡、发育和分化。它们的转录活性受甲状腺激素3，3‘，5-三碘-L-甲状腺原氨酸(T3)的调节。本研究评估了细胞质T3对转录调节因子转录反应的调节作用。在人绒毛膜癌JEG-3和猴COS-1细胞中，胞浆甲状腺激素结合蛋白是四聚体丙酮酸激酶M2亚型的单体，不与T3结合。体内单体-四聚体的相互转化受葡萄糖通过1，6-二磷酸果糖调节。在生理T3浓度下，降低葡萄糖浓度会导致胞质甲状腺激素结合蛋白的细胞浓度升高。通过使用瞬时转基因系统，在两种细胞系中都检测到伴随着人β1甲状腺激素受体转录活性的降低。在没有葡萄糖的情况下，人β1甲状腺激素受体在JEG-3和COS-1细胞中的转录活性分别降低了65%-75%和90%-95%。然而，葡萄糖对基础转录活性没有影响。这些发现证明了核前的一个重要步骤，在调节基因调节活性的TRs。
Thyroid hormone receptors (TRs) are members of the steroid hormone/retinoic acid receptor superfamily, which regulate homeostasis, development, and differentiation. Their transcriptional activity is modulated by the thyroid hormone 3,3',5-triiodo-L-thyronine (T3). The present study evaluated the effect of the availability of cytoplasmic T3 on the modulation of transcriptional responses of the TRs. In human choriocarcinoma JEG-3 and monkey COS-1 cells, the cytosolic thyroid hormone binding protein is a monomer of the tetrameric pyruvate kinase, subtype M2, which does not bind T3. The in vivo monomer-tetramer interconversion is regulated by glucose via fructose 1,6-bisphosphate. At the physiological T3 concentration, lowering the glucose concentration led to an increase in the cellular concentration of the cytosolic thyroid hormone binding protein. By using a transient transfection system, a concomitant reduction in the transcriptional activity of the human beta 1 thyroid hormone receptor was detected in both cell lines. In the absence of glucose, the transcriptional activity of the human beta 1 thyroid hormone receptor in JEG-3 and COS-1 cells was reduced by 65-75% and 90-95%, respectively. However, glucose had no effect on the basal transcriptional activity. These findings demonstrate an important prenuclear step in the modulation of the gene regulating activity of the TRs.