Thyroid hormone receptor-associated proteins and general positive cofactors mediate thyroid hormone receptor function in the absence of the TATA box-binding protein-associated factors of TFIID
Thyroid hormone receptor-associated proteins and general positive cofactors mediate thyroid hormone receptor function in the absence of the TATA box-binding protein-associated factors of TFIID
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DOI：
10.1073/pnas.96.5.1959
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发表时间：
1999-03-02
影响因子：
11.1
通讯作者：
Roeder, RG
中科院分区：
文献类型：
--
作者：
Fondell, JD;Guermah, M;Roeder, RG
先前涉及甲状腺激素受体（TR）配体依赖性激活功能的共激活因子包括p300和creb结合蛋白（CBP），类固醇受体共激活因子-1 （SRC-1）相关蛋白家族，以及多组分TR相关蛋白（TRAP）复合物。本研究表明，在用纯化因子和DNA模板重建的体外系统中，来自上游刺激活性（USA）辅因子部分的两个阳性辅因子（PC2和PC4）协同作用介导甲状腺激素（T-3）依赖性激活，无论是通过TR还是通过TR- trap复合物。值得注意的是，trap介导的TR激活增强不需要TFIID的TATA盒结合蛋白相关因子。此外，在TR-TRAP复合体或体外分析系统的其他组分中，既没有检测到多效共激活因子CBP和p300，也没有检测到SRC-1家族成员。这些结果表明，TRAP共激活因子与一般共激活因子PC2和PC4的协同作用增强了裸DNA模板水平上的TR激活，并进一步表明TFIID中TRAP和TATA盒结合蛋白相关因子之间存在潜在的功能冗余。结合早期对其他核受体相互作用辅助因子的研究，本研究还提出了激素应答基因激活的多步骤途径，涉及不同的辅助因子集。
Coactivators previously implicated in ligand-dependent activation functions by thyroid hormone receptor (TR) include p300 and CREB-binding protein (CBP), the steroid receptor coactivator-1 (SRC-1)-related family of proteins, and the multicomponent TR-associated protein (TRAP) complex. Here we show that two positive cofactors (PC2 and PC4) derived from the upstream stimulatory activity (USA) cofactor fraction act synergistically to mediate thyroid hormone (T-3)-dependent activation either by TR or by a TR-TRAP complex in an in vitro system reconstituted with purified factors and DNA templates. Significantly, the TRAP-mediated enhancement of activation by TR does not require the TATA box-binding protein-associated factors of TFIID. Furthermore, neither the pleiotropic coactivators CBP and p300 nor members of the SRC-1 family were detected in either the TR-TRAP complex or the other components of the in vitro assay system. These results show that activation by TR at the level of naked DNA templates is enhanced by cooperative functions of the TRAP coactivators and the general coactivators PC2 and PC4, and they further indicate a potential functional redundancy between TRAPs and TATA box-binding protein-associated factors in TFIID. In conjunction with earlier studies on other nuclear receptor interacting cofactors, the present study also suggests a multistep pathway, involving distinct sets of cofactors, for activation of hormone responsive genes.