Division of Neuroanatomy, Department of Neuroscience, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
Exp Cell Res. 2011 Jul 15;317(12):1689-700. doi: 10.1016/j.yexcr.2011.05.004. Epub 2011 May 14.
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/STBs 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/STBs, 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/STBs 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/STBs translocated into the nucleus, whereas the receptors colocalized with HAP1/STBs persisted in their colocalization even after treatment with their ligands. Therefore, HAP1/STBs may be involved in cytoplasmic modifications of the nuclear translocation of GR and AR in a ubiquitin-proteasome system.
石状体（STB）是一种包含亨廷顿相关蛋白 1（HAP1）的细胞质内含物，并且 HAP1/STB 的形成是通过将 HAP1 基因转染到培养的细胞中诱导的。在本研究中，我们在 COS-7 细胞中转染 HAP1 和每种受体后，检查了 HAP1/STB 与甾体激素受体（SHR），包括雄激素受体（AR）、雌激素受体、糖皮质激素受体（GR）和盐皮质激素受体的细胞内共定位。我们发现所有 SHR 的 C 末端配体结合结构域都有可能与 HAP1/STB 共定位，而只有当每个全长 SHR 与 HAP1 共表达时，AR 和 GR 才与 HAP1/STB 明显共定位。此外，似乎 HAP1/STB 不会破坏 GR 和 AR 的功能，因为 HAP1/STB 上的受体在响应其特定配体时保持核易位活性。当用蛋白酶体抑制剂处理细胞时，GR 和 AR 从 HAP1/STB 定位到细胞核外，而与 HAP1/STB 共定位的受体即使在用其配体处理后仍保持共定位。因此，HAP1/STB 可能参与了 GR 和 AR 核易位的泛素-蛋白酶体系统中的细胞质修饰。
