A thyroid hormone receptor coactivator negatively regulated by the retinoblastoma protein
A thyroid hormone receptor coactivator negatively regulated by the retinoblastoma protein
复制标题
DOI：
10.1073/pnas.94.17.9040
复制
发表时间：
1997-08-19
影响因子：
11.1
通讯作者：
Lee, WH
中科院分区：
文献类型：
--
作者：
Chang, KH;Chen, YM;Lee, WH
视网膜母细胞瘤蛋白（retinoblastoma protein，Rb）在细胞增殖、分化和发育中起着关键作用。为了在分子水平上解释Rb的功能机制，我们系统地表征了许多Rb相互作用蛋白，其中包括本文描述的克隆C5，其编码1，978个氨基酸的蛋白，估计分子量为230 kDa，相应的基因被分配到染色体14q31，同一区域的遗传变异与甲状腺激素反应的几种异常有关，该蛋白使用两个不同的区域分别结合Rb和甲状腺激素受体（TR），因此被命名为Trip230。Trip230不依赖于甲状腺激素而与Rb结合，同时它以甲状腺激素依赖性方式与TR形成复合物。蛋白质Trip230在细胞中的异位表达，但不是不与TR结合的突变形式，特异性增强TR依赖性转录活性。这些结果不仅鉴定了调节TR活性的共激活分子，而且揭示了Rb在应答甲状腺激素的途径中的作用。
The retinoblastoma protein (Rb) plays a critical role in cell proliferation, differentiation, and development, To decipher the mechanism of Rb function at the molecular level, we have systematically characterized a number of Rb-interacting proteins, among which is the clone C5 described here, which encodes a protein of 1,978 amino acids with an estimated molecular mass of 230 kDa, The corresponding gene was assigned to chromosome 14q31, the same region where genetic alterations have been associated with several abnormalities of thyroid hormone response, The protein uses two distinct regions to bind Rb and thyroid hormone receptor (TR), respectively, and thus mas named Trip230, Trip230 binds to Rb independently of thyroid hormone while it forms a complex with TR in a thyroid hormone-dependent manner, Ectopic expression of the protein Trip230 in cells, but not a mutant form that does not bind to TR, enhances specifically TR-dependent transcriptional activity, Coexpression of wild-type Rb, but not mutant Rb that fails to bind to Trip230, inhibits such activity, These results not only identify a coactivator molecule that modulates TR activity, but also uncover a role for Rb in a pathway that responds to thyroid hormone.