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Nucleocytoplasmic shuttling of the glucocorticoid receptor is influenced by tetratricopeptide repeat-containing proteins.
Journal of Cell Science ( IF 3.3 ) Pub Date : 2020-06-16 , DOI: 10.1242/jcs.238873
Gisela I Mazaira 1 , Pablo C Echeverria 2 , Mario D Galigniana 3, 4
Affiliation  

Gisela I. Mazaira, Pablo C. Echeverria, and Mario D. Galigniana

It has been demonstrated that tetratricopeptide-repeat (TPR) domain proteins regulate the subcellular localization of glucocorticoid receptor (GR). This study analyses the influence of the TPR domain of high molecular weight immunophilins in the retrograde transport and nuclear retention of GR. Overexpression of the TPR peptide prevented efficient nuclear accumulation of the GR by disrupting the formation of complexes with the dynein-associated immunophilin FKBP52 (also known as FKBP4), the adaptor transporter importin-β1 (KPNB1), the nuclear pore-associated glycoprotein Nup62 and nuclear matrix-associated structures. We also show that nuclear import of GR was impaired, whereas GR nuclear export was enhanced. Interestingly, the CRM1 (exportin-1) inhibitor leptomycin-B abolished the effects of TPR peptide overexpression, although the drug did not inhibit GR nuclear export itself. This indicates the existence of a TPR-domain-dependent mechanism for the export of nuclear proteins. The expression balance of those TPR domain proteins bound to the GR–Hsp90 complex may determine the subcellular localization and nucleocytoplasmic properties of the receptor, and thereby its pleiotropic biological properties in different tissues and cell types.



中文翻译:

糖皮质激素受体的核细胞质穿梭受到含有四三肽重复序列的蛋白质的影响。

吉塞拉·I·马扎伊拉、巴勃罗·C·埃切维里亚和马里奥·D·加利尼亚纳

已证明四三肽重复(TPR)结构域蛋白调节糖皮质激素受体(GR)的亚细胞定位。本研究分析了高分子量亲免素的TPR结构域对GR逆行转运和核滞留的影响。TPR 肽的过度表达通过破坏与动力蛋白相关的亲免蛋白 FKBP52(也称为 FKBP4)、衔接转运蛋白 importin-β1(KPNB1)、核孔相关糖蛋白 Nup62 和核基质相关结构。我们还表明,GR 的核进口受到损害,而 GR 的核出口则得到增强。有趣的是,CRM1 (exportin-1) 抑制剂 leptomycin-B 消除了 TPR 肽过度表达的影响,尽管该药物本身并不抑制 GR 核输出。这表明存在 TPR 结构域依赖性核蛋白输出机制。与 GR-Hsp90 复合物结合的 TPR 结构域蛋白的表达平衡可能决定受体的亚细胞定位和核质特性,从而决定其在不同组织和细胞类型中的多效性生物学特性。

更新日期:2020-06-30
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