The underlying mechanism of orphan nuclear receptor estrogen-related receptor α (ERRα) in breast cancer was investigated by identifying its interaction partners using mass spectrometry. F-box and leucine-rich repeat protein 10 (FBXL10), which modulates various physiological processes, may interact with ERRα in breast cancer. Here, we investigated the interaction between FBXL10 and ERRα, and their protein expression and correlation in breast cancer. Mechanical studies revealed that FBXL10 stabilized ERRα protein levels by reducing its poly-ubiquitylation and promoting its mono-ubiquitylation. The reporter gene assay and examination of ERRα target genes validated the increased transcriptional activity of ERRα due to its increased protein levels by FBXL10. FBXL10 also increased ERRα enrichment at the promoter region of its target genes. Functionally, FBXL10 facilitated the ERRα/peroxisome proliferator-activated receptor gamma coactivator 1 β (PGC1β)-mediated proliferation and tumorigenesis of breast cancer cells in vitro and in vivo. Our results uncovered a molecular mechanism linking the mono-ubiquitylation and protein stability of ERRα to functional interaction with FBXL10. Moreover, a novel regulatory axis of FBXL10 and ERRα regulating the proliferation and tumorigenesis of breast cancer cells was established.

孤儿核受体雌激素相关受体α（ERRα）在乳腺癌中的潜在机制通过使用质谱法鉴定其相互作用伙伴来研究。F-box 和富含亮氨酸的重复蛋白 10 (FBXL10) 可调节各种生理过程，可能与乳腺癌中的 ERRα 相互作用。在这里，我们研究了 FBXL10 和 ERRα 之间的相互作用，以及它们在乳腺癌中的蛋白质表达和相关性。力学研究表明，FBXL10 通过减少其多泛素化和促进其单泛素化来稳定 ERRα 蛋白水平。报告基因测定和 ERRα 靶基因的检查证实了 ERRα 的转录活性增加，因为它通过 FBXL10 增加了蛋白质水平。FBXL10 还增加了其靶基因启动子区域的 ERRα 富集。在功能上，体外和体内。我们的结果揭示了将 ERRα 的单泛素化和蛋白质稳定性与与 FBXL10 的功能相互作用联系起来的分子机制。此外，建立了一个新的调节轴 FBXL10 和 ERRα 调节乳腺癌细胞的增殖和肿瘤发生。