Institut de Génomique Fonctionnelle de Lyon, Universitéde Lyon, Université Lyon 1, CNRS, INRA, Ecole Normale Supérieure de Lyon, 46 allée d'Italie, 69364 Lyon Cedex 07, France.
BMC Mol Biol. 2010 Jan 15;11:3. doi: 10.1186/1471-2199-11-3.
The transcriptional activity of Nuclear hormone Receptors (NRs) is regulated by interaction with coactivator or corepressor proteins. Many of these cofactors have been shown to have a misregulated expression or to show a subcellular mislocalization in cancer cell lines or primary tumors. Therefore they can be factors involved in the process of oncogenesis.
We describe a novel NR coregulator, TACC1, which belongs to the Transforming Acidic Coiled Coil (TACC) family. The interaction of TACC1 with Thyroid Hormone Receptors (TR) and several other NRs has been shown in a yeast two-hybrid screen and confirmed by GST pulldown, colocalization and co-immunoprecipitation experiments. TACC1 interacts preferentially with unliganded NRs. In F9 cells, endogenous TACC1 localized in the chromatin-enriched fraction of the nucleus and interacted with Retinoid Acid Receptors (RARalpha) in the nucleus. TACC1 depletion in the cell led to decreased RARalpha and TRalpha ligand-dependent transcriptional activity and to delocalization of TR from the nucleus to the cytoplasm.
From these experimental studies we propose that TACC1 might be a scaffold protein building up a transcriptional complex around the NRs we studied. This function of TACC1 might account for its involvement in several forms of tumour development.
核受体（NRs）的转录活性受与共激活因子或核心抑制蛋白相互作用的调节。许多这些辅助因子的表达已经被证明失调，或者在癌细胞系或原发性肿瘤中表现出亚细胞定位错误。因此，它们可以是参与致癌过程的因素。
我们描述了一种新型的 NR 共调节因子 TACC1，它属于转化酸性卷曲螺旋（TACC）家族。TACC1 与甲状腺激素受体（TR）和其他几种 NR 的相互作用已在酵母双杂交筛选中得到证实，并通过 GST 下拉、共定位和共免疫沉淀实验得到确认。TACC1 优先与未配体结合的 NR 相互作用。在 F9 细胞中，内源性 TACC1 定位于富含染色质的核区，并与核内视黄酸受体（RARalpha）相互作用。细胞中 TACC1 的耗竭导致 RARalpha 和 TRalpha 配体依赖性转录活性降低，TR 从核内易位到细胞质。
从这些实验研究中，我们提出 TACC1 可能是一种支架蛋白，围绕我们研究的 NR 构建转录复合物。TACC1 的这种功能可能解释了它参与多种形式的肿瘤发生。
