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首页> 外文期刊>Molecular and Cellular Biology >Heat Shock Protein 27 Is Required for Sex Steroid Receptor Trafficking to and Functioning at the Plasma Membrane
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Heat Shock Protein 27 Is Required for Sex Steroid Receptor Trafficking to and Functioning at the Plasma Membrane

机译：性激素转运到血浆膜并在其上起作用需要热激蛋白27。

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Classical sex steroid receptors (SRs) localize at the plasma membranes (PMs) of cells, initiating signal transduction through kinase cascades that contribute to steroid hormone action. Palmitoylation of the SRs is required for membrane localization and function, but the proteins that facilitate this modification and subsequent receptor trafficking are unknown. Initially using a proteomic approach, we identified that heat shock protein 27 (Hsp27) binds to a motif in estrogen receptor alpha (ERα) and promotes palmitoylation of the SR. Hsp27-induced acylation occurred on the ERα monomer and augmented caveolin-1 interactions with ERα, resulting in membrane localization, kinase activation, and DNA synthesis in breast cancer cells. Oligomerization of Hsp27 was required, and similar results were found for the trafficking of endogenous progesterone and androgen receptors to the PMs of breast and prostate cancer cells, respectively. Small interfering RNA (siRNA) knockdown of Hsp27 prevented sex SR trafficking to and signaling from the membrane. These results identify a conserved and novel function for Hsp27 with potential as a target for interrupting signaling from membrane sex SRs to tumor biology in hormone-responsive cancers.
机译：经典的性类固醇受体（SR）定位在细胞的质膜（PM）处，通过有助于类固醇激素作用的激酶级联反应启动信号转导。 SR的棕榈酰化是膜定位和功能所必需的，但是促进这种修饰和随后受体转运的蛋白尚不清楚。最初使用蛋白质组学方法，我们发现热激蛋白27（Hsp27）与雌激素受体α（ERα）中的基序结合并促进SR的棕榈酰化。 Hsp27诱导的酰化作用发生在ERα单体上，并且增强了Caveolin-1与ERα的相互作用，导致了乳腺癌细胞中的膜定位，激酶激活和DNA合成。 Hsp27的寡聚化是必需的，对于将内源性孕激素和雄激素受体分别转运至乳腺癌和前列腺癌细胞的PMs，也发现了相似的结果。 Hsp27的小分子干扰RNA（siRNA）敲低阻止了性SR转运到膜并从膜发出信号。这些结果确定了Hsp27的保守和新颖功能，具有潜在的作为靶标，可中断激素反应性癌症中从膜性SRs到肿瘤生物学的信号传导的靶标。

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