Chang K H, Chen Y, Chen T T, Chou W H, Chen P L, Ma Y Y, Yang-Feng T L, Leng X, Tsai M J, O'Malley B W, Lee W H
Department of Molecular Medicine and Institute of Biotechnology, University of Texas Health Science Center at San Antonio, 15355 Lambda Drive, San Antonio, TX 78245, USA.
Proc Natl Acad Sci U S A. 1997 Aug 19;94(17):9040-5. doi: 10.1073/pnas.94.17.9040.
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 was 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.
视网膜母细胞瘤蛋白（Rb）在细胞增殖、分化和发育过程中发挥着关键作用。为了在分子水平上解析Rb的功能机制，我们系统地表征了许多与Rb相互作用的蛋白，其中包括这里描述的克隆C5，它编码一种含有1978个氨基酸、估计分子量为230 kDa的蛋白。相应的基因定位于14号染色体q31区域，该区域的基因改变与甲状腺激素反应的多种异常有关。该蛋白分别利用两个不同的区域与Rb和甲状腺激素受体（TR）结合，因此被命名为Trip230。Trip230不依赖甲状腺激素与Rb结合，而以甲状腺激素依赖的方式与TR形成复合物。在细胞中异位表达蛋白Trip230，而非不与TR结合的突变体形式，可特异性增强TR依赖的转录活性。共表达野生型Rb，而非不能与Trip230结合的突变型Rb，可抑制这种活性。这些结果不仅鉴定出一种调节TR活性的共激活分子，还揭示了Rb在甲状腺激素反应途径中的作用。
