GOLM1 promotes prostate cancer progression via interaction with PSMD1 and enhancing AR ‐driven transcriptional activation

作者：Guang Yan, Tianhang Zhu, Jiawei Zhou, Xia Li, Zonghua Wen, Bahaerguli Miuhuitijiang, Zhiyong Zhang, Yuejun Du, Cheng-Yao Li, Xiaojun Shi, Wan-Ling Tan · 发表于：Journal of Cellular and Molecular Medicine · 年份：2024 · DOI：10.1111/jcmm.70186 · 被引用次数：2 · 研究领域：Prostate Cancer Treatment and Research、Ubiquitin and proteasome pathways、Prostate Cancer Diagnosis and Treatment

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.