HETERODIMERIZATION AMONG THYROID-HORMONE RECEPTOR, RETINOIC ACID RECEPTOR, RETINOID-X RECEPTOR, CHICKEN OVALBUMIN UPSTREAM PROMOTER TRANSCRIPTION FACTOR, AND AN ENDOGENOUS LIVER PROTEIN
HETERODIMERIZATION AMONG THYROID-HORMONE RECEPTOR, RETINOIC ACID RECEPTOR, RETINOID-X RECEPTOR, CHICKEN OVALBUMIN UPSTREAM PROMOTER TRANSCRIPTION FACTOR, AND AN ENDOGENOUS LIVER PROTEIN
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DOI：
10.1210/me.6.9.1468
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发表时间：
1992-09-01
影响因子：
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通讯作者：
LAZAR, MA
中科院分区：
文献类型：
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作者：
BERRODIN, TJ;MARKS, MS;LAZAR, MA
甲状腺激素受体（TR）以单体、同型二聚体和异源二聚体与核蛋白结合。我们已经证实，TR可以与类视黄醇X受体(RXRs)- α和- β形成异二聚体，并且发现核受体超家族的另一个成员，鸡卵白蛋白上游启动子转录因子（COUP-TF）也可以与TR结合回文甲状腺激素应答元件（TREp）形成异二聚体。利用特异性抗体超移了COUP-TF/TR DNA复合物，证实了COUP-TF和TR之间的相互作用。肝脏中TR与主要TR异源二聚化伙伴之间的复合物不受COUP-TF和RXRbeta抗体的影响，但被抗rxrα抗体超移，表明肝脏蛋白与rxrα高度相关。事实上，TR/RXR和TR/肝蛋白异源二聚体在TREp中接触相同的胍残基。在肝脏中，视黄酸受体（RAR）也与COUP-TF以及rxrα、rxrβ和TR异二聚体发生异二聚。与其与TR和RAR异源二聚体的能力相反，在与TREp结合的情况下，我们没有检测到COUP-TF与rxrα、rxrβ或肝核蛋白之间的异源二聚体。这些结果表明肝脏中主要的TR异二聚化伙伴与rxrα高度相关，但其他核受体如COUP-TF可以与TR和RAR异二聚化，提示选择性蛋白-蛋白相互作用可能参与了激素作用的组织和靶基因特异性。
Thyroid hormone receptor (TR) binds to DNA as a monomer, homodimer, and heterodimer with nuclear proteins. We have confirmed that the TR can heterodimerize with retinoid X receptors (RXRs)-alpha and -beta, and have found that another member of the nuclear receptor superfamily, chicken ovalbumin upstream promoter transcription factor (COUP-TF), also formed heterodimers with the TR in the context of binding to a palindromic thyroid hormone-responsive element (TREp). The interaction between COUP-TF and the TR was confirmed using specific antibodies which supershifted the COUP-TF/TR DNA complexes. The complex between the TR and the major TR heterodimerization partner in liver was unaffected by antibodies to COUP-TF and RXRbeta, but was supershifted by an anti-RXRalpha antibody, indicating that the liver protein is highly related to RXRalpha. Indeed, the TR/RXR and TR/liver protein heterodimers contact the same guanidine residues in TREp. The retinoic acid receptor (RAR) also heterodimerized with COUP-TF as well as with RXRalpha, RXRbeta, and the TR heterodimerization partner in liver. In contrast to its ability to heterodimerize with the TR and RAR, we did not detect heterodimers between COUP-TF and either RXRalpha, RXRbeta, or the liver nuclear protein in the context of binding to the TREp. These results show that the major TR heterodimerization partner in liver is highly related to RXRalpha, but that other nuclear receptors such as COUP-TF can heterodimerize with the TR and RAR, suggesting that selective protein-protein interactions may be involved in the tissue and target gene specificities of hormone action.