Role of molecular chaperones and TPR-domain proteins in the cytoplasmic transport of steroid receptors and their passage through the nuclear pore.
Role of molecular chaperones and TPR-domain proteins in the cytoplasmic transport of steroid receptors and their passage through the nuclear pore.
复制标题
DOI：
10.4161/nucl.1.4.11743
复制
发表时间：
2010-07
期刊：
影响因子：
--
通讯作者：
Piwien-Pilipuk G
中科院分区：
文献类型：
--
作者：
Galigniana MD;Echeverría PC;Erlejman AG;Piwien-Pilipuk G
在缺乏激素的情况下，糖皮质激素受体和盐皮质激素受体等激素受体主要位于细胞质中。一旦类固醇结合，它们就会迅速积聚在细胞核中。无论它们的主要位置如何，这些受体和许多其他核因子都经历了持续和动态的核质穿梭。类固醇受体家族的所有成员都形成了大的寡聚结构，包括90 kDa(HSP90)和70 kDa(HSP70)的热休克蛋白，小的酸性蛋白p23，以及四肽重复(TPR)结构域的蛋白，如FK506结合蛋白(FKBPs)，亲环素(Cyps)或丝氨酸/苏氨酸蛋白磷酸酶5(PP5)。人们一直认为，伴侣异质复合体的解离(这一过程通常被称为受体“转化”)是允许类固醇受体核进口的第一步。然而，实验证据与一个模型是一致的，该模型认为，受体通过细胞质的反向运输需要伴侣机制，并且也有助于通过核孔。最近的证据表明，以热休克蛋白90为基础的伴侣系统还与核孔结构相互作用，如Importinβ和完整的核孔糖蛋白Nup62，促进未转化的受体通过核孔。
In the absence of hormone, corticosteroid receptors such as GR (glucocorticoid receptor) and (mineralocorticoid receptor) are primarily located in the cytoplasm. Upon steroid-binding, they rapidly accumulate in the nucleus. Regardless of their primary location, these receptors and many other nuclear factors undergo a constant and dynamic nucleocytoplasmic shuttling. All members of the steroid receptor family are known to form large oligomeric structures with the heat-shock proteins of 90-kDa (hsp90) and 70-kDa (hsp70), the small acidic protein p23, and a tetratricopeptide repeat (TPR) -domain protein such as FK506-binding proteins (FKBPs), cyclophilins (CyPs) or the serine/threonine protein phosphatase 5 (PP5). It has always been stated that the dissociation of the chaperone heterocomplex (a process normally referred to as receptor “transformation”) is the first step that permits the nuclear import of steroid receptors. However the experimental evidence is consistent with a model where the chaperone machinery is required for the retrotransport of the receptor through the cytoplasm and also facilitates the passage through the nuclear pore. Recent evidence indicates that the hsp90-based chaperone system also interacts with structures of the nuclear pore such as importin β and the integral nuclear pore glycoprotein Nup62 facilitating the passage of the untransformed receptor through the nuclear pore.