EVIDENCE THAT THE FK506-BINDING IMMUNOPHILIN HEAT-SHOCK-PROTEIN-56 IS REQUIRED FOR TRAFFICKING OF THE GLUCOCORTICOID RECEPTOR FROM THE CYTOPLASM TO THE NUCLEUS
EVIDENCE THAT THE FK506-BINDING IMMUNOPHILIN HEAT-SHOCK-PROTEIN-56 IS REQUIRED FOR TRAFFICKING OF THE GLUCOCORTICOID RECEPTOR FROM THE CYTOPLASM TO THE NUCLEUS
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DOI：
10.1210/me.9.11.1549
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发表时间：
1995-11-01
影响因子：
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通讯作者：
PRATT, WB
中科院分区：
文献类型：
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作者：
CZAR, MJ;LYONS, RH;PRATT, WB
FK506 结合亲免蛋白 hsp56 (FKBP52) 是与多蛋白杂复合物中未转化的类固醇受体相关的几种伴侣蛋白之一。热休克蛋白 56 (hsp56) 在受体作用方面的功能尚不清楚，糖皮质激素受体异质复合物组装或受体激素结合结构域正确折叠成高亲和力类固醇结合构象不需要 hsp56，在完整细胞中，大部分 hsp56 位于细胞核中，少数与细胞质中的微管共定位，hsp56 包含一个保守的带负电荷的结构域，我们推测可能作为核定位信号识别序列。在这里，我们表明，将针对该负序列产生的抗体注射到完整的L细胞中会阻止随后地塞米松介导的糖皮质激素受体向细胞核的转移。非免疫兔血清和针对 hsp56 上另一个位点产生的抗体不会影响受体运动。与纯化的 hsp56 预孵育可阻断针对负序列的 419 抗体对受体运动的抑制，但与纯化的 hsp90、hsp70 或 BSA 预孵育则不会阻断。这些观察结果与 hsp56 参与受体转运至细胞核的可能性一致，可能充当核定位信号识别蛋白。 FK506 不影响受体向细胞核的运输，表明 hsp56 的肽基脯氨酰异构酶活性不受影响。
The FK506-binding immunophilin hsp56 (FKBP52) is one of several chaperone proteins associated with untransformed steroid receptors in a multiprotein heterocomplex. The function of heat shock protein 56 (hsp56) with respect to receptor action is unknown, hsp56 is not required for glucocorticoid receptor heterocomplex assembly or for proper folding of the receptor hormone-binding domain into a high affinity steroid-binding conformation, In intact cells, the majority of the hsp56 is located in the nucleus, with a minority colocalizing with microtubules in the cytoplasm, hsp56 contains a conserved negatively charged domain that we speculate might serve as a nuclear localization signal recognition sequence. Here we show that injection of an antibody raised against this negative sequence into intact L cells impedes subsequent dexamethasone-mediated shift of the glucocorticoid receptor into the nucleus. Nonimmune rabbit serum and an antibody raised against another site on hsp56 do not affect receptor movement, Inhibition of receptor movement by the 419 antibody against the negative sequence is blocked by preincubation with purified hsp56, but not by preincubation with purified hsp90, hsp70, or BSA. These observations are consistent with the possibility that hsp56 is involved in receptor trafficking to the nucleus, possibly functioning as the nuclear localization signal recognition protein. Receptor trafficking to the nucleus is not affected by FK506, indicating that the peptidylprolyl isomerase activity of hsp56 is not involved.