GOLM1 通过与 PSMD1 相互作用并增强 AR 驱动的转录激活,促进前列腺癌的进展。

Guang Yan, Tianhang Zhu, Jiawei Zhou, Xia Li, Zonghua Wen, Bahaerguli Miuhuitijiang, Zhiyong Zhang, Yuejun Du, Chengyao Li, Xiaojun Shi, Wanlong Tan
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引用次数: 0

摘要

雄激素受体(AR)的异常转录激活是前列腺癌(PCa)的主要病因,包括初期和雄激素依赖性阶段。我们的研究表明,高尔基体膜蛋白1(GOLM1)是PCa进展过程中AR驱动的转录活性的关键调节因子。利用本地临床数据和 TCGA 数据,我们建立了 GOLM1 与 AR 靶基因之间的紧密联系,并进一步证明了 GOLM1 可以增强 AR 靶基因的表达。通过质谱分析和 Co-IP 分析,我们发现 GOLM1 与 26S 蛋白酶体中 19S 调控复合物的组成部分 PSMD1 相互作用。众所周知,泛素蛋白酶体在 AR 表达和转录调控中发挥着重要作用。我们的研究结果表明,GOLM1 通过与 PSMD1 结合增强了泛素蛋白酶体的活性,从而促进了 AR 驱动的转录活性和 PCa 的进展。这些结果表明,GOLM1 及其相关蛋白可能成为以 AR 驱动的转录激活失调为特征的 PCa 的潜在治疗靶点。
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GOLM1 promotes prostate cancer progression via interaction with PSMD1 and enhancing AR-driven transcriptional activation

Aberrant transcriptional activation of the androgen receptor (AR) is a predominant cause of prostate cancer (PCa), including both in the initial and androgen-independent stages. Our study highlights Golgi membrane protein 1 (GOLM1) as a key regulator of AR-driven transcriptional activity in PCa progression. Utilizing local clinical data and TCGA data, we have established a robust association between GOLM1 and AR target genes, and further demonstrated that GOLM1 can enhance the expression of AR target genes. We discovered that GOLM1 interacts with PSMD1, a component of the 19S regulatory complex in the 26S proteasome, using mass spectrometry and Co-IP analysis. It is well known that ubiquitin-proteasome plays a vital role in AR expression and transcriptional regulation. Our findings demonstrate that GOLM1 enhances ubiquitin proteasome activity by binding to PSMD1, thereby facilitating AR-driven transcriptional activity and PCa progression. These results indicate that GOLM1 and its associated proteins may become potential therapeutic targets for PCa characterized by dysregulated AR-driven transcriptional activation.

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期刊介绍: The Journal of Cellular and Molecular Medicine serves as a bridge between physiology and cellular medicine, as well as molecular biology and molecular therapeutics. With a 20-year history, the journal adopts an interdisciplinary approach to showcase innovative discoveries. It publishes research aimed at advancing the collective understanding of the cellular and molecular mechanisms underlying diseases. The journal emphasizes translational studies that translate this knowledge into therapeutic strategies. Being fully open access, the journal is accessible to all readers.
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