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首页> 外文期刊>Molecular and Cellular Biology >Selective Estrogen Receptor Modulators 4-Hydroxytamoxifen and Raloxifene Impact the Stability and Function of SRC-1 and SRC-3 Coactivator Proteins
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Selective Estrogen Receptor Modulators 4-Hydroxytamoxifen and Raloxifene Impact the Stability and Function of SRC-1 and SRC-3 Coactivator Proteins

机译：选择性雌激素受体调节剂4-羟基他莫昔芬和雷洛昔芬影响SRC-1和SRC-3共激活蛋白的稳定性和功能

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Proteasome-mediated protein degradation has been implicated in playing a role in nuclear receptor-mediated gene expression; inhibition of the proteasome impairs the transcriptional activity of estrogen receptor α (ERα) and most other nuclear receptors. This coincides with blockage of agonist-dependent degradation of the receptor and elevation of the steady-state levels of SRC family coactivators and CBP. Here, we examined the effects that different ERα ligands have on coactivator protein steady-state levels and demonstrate that the selective ER modulators (SERMs) 4-hydroxytamoxifen (4HT) and raloxifene are able to elevate SRC-1 and SRC-3 protein levels. Using the HeLa cell line, we show that this effect is ERα dependent. Consistent with the observed increase in coactivator protein levels, we were also able to observe an increase in the transcriptional activity of other nuclear receptors in SERM-treated cells. Information presented here demonstrates an unexpected consequence of SERM treatment, which could help further define the complex tissue responses to 4HT and raloxifene, and suggests that these ligands can have a broad biological action, stimulating the transcriptional activity of other nuclear receptors.
机译：蛋白酶体介导的蛋白质降解与核受体介导的基因表达有关。蛋白酶体的抑制削弱了雌激素受体α（ERα）和大多数其他核受体的转录活性。这与受体激动剂依赖性降解的阻滞和SRC家族共激活剂和CBP稳态水平的升高相吻合。在这里，我们检查了不同ERα配体对共激活蛋白稳态水平的影响，并证明了选择性ER调节剂（SERM）4-羟基他莫昔芬（4HT）和雷洛昔芬能够提高SRC-1和SRC-3蛋白水平。使用HeLa细胞系，我们证明这种效应是ERα依赖性的。与观察到的共激活蛋白水平的增加一致，我们还能够观察到SERM处理的细胞中其他核受体的转录活性增加。本文提供的信息证明了SERM治疗的出乎意料的结果，可以帮助进一步定义复杂的组织对4HT和雷洛昔芬的反应，并暗示这些配体可以具有广泛的生物学作用，刺激其他核受体的转录活性。

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