Intracellular colocalization of HAP1/STBs with steroid hormone receptors and its enhancement by a proteasome inhibitor
Intracellular colocalization of HAP1/STBs with steroid hormone receptors and its enhancement by a proteasome inhibitor
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DOI：
10.1016/j.yexcr.2011.05.004
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发表时间：
2011-07-15
影响因子：
3.7
通讯作者：
Shinoda, Koh
中科院分区：
文献类型：
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作者：
Fujinaga, Ryutaro;Takeshita, Yukio;Shinoda, Koh
stimoid body （STB）是含有亨廷顿蛋白相关蛋白1 （HAP1）的细胞质包涵体，HAP1/STB的形成是通过将HAP1基因转染到培养细胞中诱导的。在本研究中，我们在共转染HAP1和每种受体的COS-7细胞中检测了HAP1/STB5与类固醇激素受体（SHRs）的细胞内共定位，包括雄激素受体（AR）、雌激素受体、糖皮质激素受体（GR）和矿化皮质激素受体。我们发现所有SHR的c端配体结合域都有与HAP1/STB5共定位的潜力，而当每个全长SHR与HAP1共表达时，只有AR和GR与HAP1/ stb明确共定位。此外，HAP1/STB5似乎没有破坏GR和AR功能，因为HAP1/ stb上的受体对其特定配体的反应维持核易位活性。当用蛋白酶体抑制剂处理细胞时，定位于HAP1/STB5外的GR和AR易位到细胞核中，而与HAP1/STB5共定位的受体即使在其配体处理后仍能维持其共定位。因此，HAP1/STB5可能参与了泛素-蛋白酶体系统中GR和AR核易位的细胞质修饰。(c) 2011爱思唯尔公司版权所有。
The stigmoid body (STB) is a cytoplasmic inclusion containing huntingtin-associated protein 1 (HAP1), and HAP1/STB formation is induced by transfection of the HAP1 gene into cultured cells. In the present study, we examined the intracellular colocalization of HAP1/STB5 with steroid hormone receptors (SHRs), including the androgen receptor (AR), estrogen receptor, glucocorticoid receptor (GR), and mineralocorticoid receptor, in COS-7 cells cotransfected with HAP1 and each receptor. We found that C-terminal ligand-binding domains of all SHRs had potential for colocalization with HAP1/STB5, whereas only AR and GR were clearly colocalized with HAP1/STBs when each full-length SHR was coexpressed with HAP1. In addition, it appeared that HAP1/STB5 did not disrupt GR and AR functions because the receptors on HAP1/STBs maintained nuclear translocation activity in response to their specific ligands. When the cells were treated with a proteasome inhibitor, GR and AR localized outside HAP1/STB5 translocated into the nucleus, whereas the receptors colocalized with HAP1/STB5 persisted in their colocalization even after treatment with their ligands. Therefore, HAP1/STB5 may be involved in cytoplasmic modifications of the nuclear translocation of GR and AR in a ubiquitin-proteasome system. (c) 2011 Elsevier Inc. All rights reserved.