Yen P M, Sugawara A, Chin W W
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.
J Biol Chem. 1992 Nov 15;267(32):23248-52.
Thyroid hormone receptor (TR) heterodimerizes with retinoic acid receptor (RAR), retinoid X receptor (RXR), and triiodothyronine receptor auxiliary protein (TRAP) on natural and synthetic hormone response elements. Recently we showed that triiodothyronine (T3) decreased TR homodimer, but not TR/TRAP heterodimer, binding to several thyroid hormone response elements (TREs). The effect of ligand on TR/RAR and TR/RXR heterodimer binding to DNA is not known. In this study, we showed that TR formed heterodimers with RAR and RXR on a retinoic acid (RA) response element and two TREs. Surprisingly, T3, but not RA, decreased TR/RAR heterodimer binding to DNA. In contrast, T3, all-trans-RA, or 9-cis-RA did not affect TR/RXR binding to DNA. This finding suggests that TR/RXR heterodimer is a stable receptor complex that remains bound to response elements in the presence of ligand and therefore may be a receptor complex involved in T3-regulated transcription.
甲状腺激素受体（TR）在天然和合成激素反应元件上与视黄酸受体（RAR）、视黄醇X受体（RXR）以及三碘甲状腺原氨酸受体辅助蛋白（TRAP）形成异源二聚体。最近我们发现，三碘甲状腺原氨酸（T3）会减少TR同源二聚体与多个甲状腺激素反应元件（TRE）的结合，但不会减少TR/TRAP异源二聚体与这些元件的结合。配体对TR/RAR和TR/RXR异源二聚体与DNA结合的影响尚不清楚。在本研究中，我们发现TR在视黄酸（RA）反应元件和两个TRE上与RAR和RXR形成异源二聚体。令人惊讶的是，T3而非RA会减少TR/RAR异源二聚体与DNA的结合。相反，T3、全反式视黄酸或9-顺式视黄酸均不影响TR/RXR与DNA的结合。这一发现表明，TR/RXR异源二聚体是一种稳定的受体复合物，在配体存在的情况下仍与反应元件结合，因此可能是参与T3调节转录的受体复合物。
