Chen Y, Chen P L, Chen C F, Sharp Z D, Lee W H
Department of Molecular Medicine and Institute of Biotechnology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78245-3207, USA.
Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4443-8. doi: 10.1073/pnas.96.8.4443.
Trip230 is a novel coactivator of the thyroid hormone receptor that is negatively regulated by the retinoblastoma tumor-suppressor protein. In an examination of its subcellular distribution, Trip230 localized predominantly to the vicinity of the Golgi instead of the nucleus, as other nuclear hormone receptor coactivators. Using a series of deletion mutants, a critical region identified for Golgi area targeting coincided with a previously defined thyroid hormone receptor-binding domain of Trip230. During cell cycle progression, the expression level of Trip230 is constant and a significant portion is imported into the nucleus at S phase. Within an hour of treating cells with T3, Trip230 immunofluorescence transiently colocalized with TR in prominent subnuclear structures. T3-dependent nuclear import of Trip230 does not require new protein synthesis. Coincident with T3 treatment and nuclear import, newly phosphorylated residue(s) appeared in Trip230, suggesting that phosphorylation may be involved in its nuclear import. These findings provided a novel mechanism for the regulation of nuclear hormone transcription factors by hormone-responsive phosphorylation and nuclear import of cytoplasmically located coactivators.
Trip230是一种新型的甲状腺激素受体共激活因子，受视网膜母细胞瘤肿瘤抑制蛋白的负调控。在对其亚细胞分布的研究中，Trip230主要定位于高尔基体附近而非细胞核，这与其他核激素受体共激活因子不同。通过一系列缺失突变体，确定了一个靶向高尔基体区域的关键区域，该区域与先前定义的Trip230甲状腺激素受体结合域重合。在细胞周期进程中，Trip230的表达水平恒定，并且在S期有相当一部分被导入细胞核。在用T3处理细胞一小时内，Trip230免疫荧光与TR在明显的核内亚结构中瞬时共定位。Trip230的T3依赖性核输入不需要新的蛋白质合成。与T3处理和核输入同时发生的是，Trip230中出现了新的磷酸化残基，这表明磷酸化可能参与其核输入。这些发现为激素响应性磷酸化和细胞质中共激活因子的核输入调控核激素转录因子提供了一种新机制。
