Isolation and characterization of a novel ligand-dependent thyroid hormone receptor-coactivating protein
Isolation and characterization of a novel ligand-dependent thyroid hormone receptor-coactivating protein
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DOI：
10.1074/jbc.272.47.29834
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发表时间：
1997-11-21
影响因子：
4.8
通讯作者：
Hollenberg, AN
中科院分区：
文献类型：
--
作者：
Monden, T;Wondisford, FE;Hollenberg, AN
甲状腺激素受体（TR）与T-3反应元件结合后调节靶基因的表达。在T-3存在下，TR募集共激活蛋白，既调节又整合配体反应。对推定的全长克隆的分析证明了编码大小为120 kDa的920个氨基酸的蛋白质（p120）的cDNA序列，与已知序列的比对显示与先前鉴定的功能未知的蛋白质（称为骨骼肌丰富蛋白）同源，相互作用研究表明，p120与TR AF-2结构域的配体通过111个氨基酸的区域的存在下相互作用。北方分析表明其在人体组织中广泛表达。CV-1细胞中的共转染试验表明，在T-3存在下，p120增强了TR介导的多个T-3反应元件的反式激活。此外，CREB结合蛋白与p120协同作用以增强这种作用。当与GAL 4 DNA结合域连接时，p120是单独的转录激活因子。因此，p120作为核受体共激活剂满足许多重要标准。
The thyroid hormone receptor (TR) regulates the expression of target genes upon binding to triiodothyro nine (T-3) response elements, In the presence of T-3, the TR recruits coactivating proteins that both modulate and integrate the ligand response, We report here the cloning of a novel protein using the TR ligand-binding domain as bait in the yeast two-hybrid system. Analysis of a putative full length clone demonstrates a cDNA sequence that encodes a protein of 920 amino acids with a size of 120 kDa (p120), Alignment with known sequences shows homology to a previously identified protein of unknown function, termed skeletal muscle abundant protein, Interaction studies demonstrate that p120 interacts with the TR AF-2 domain in the presence of ligand through a 111-amino acid region. Northern analysis demonstrates widespread expression in human tissues. Cotransfection assays in CV-1 cells demonstrate that p120 enhances TR-mediated transactivation on multiple T-3 response elements in the presence of T-3. In addition, CREB-binding protein synergizes with p120 to enhance this effect. When linked to the GAL4 DNA-bind ing domain, p120 is an activator of transcription alone. Thus, p120 satisfies a number of important criteria as a nuclear receptor coactivator.