Department of Reproductive Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
Adv Clin Exp Med. 2020 Oct;29(10):1153-1160. doi: 10.17219/acem/123355.
The post-translational modifications of proteins control various physiological and pathological events in cells.
In this study, we investigated the influences of the X-linked deubiquitination enzyme USP26 in mediating androgen receptor (AR) deubiquitination in the physiological events of sperm maturation and spermatogenesis through the AR signaling pathway.
The cell cycle results detected with flow cytometry (FCM) showed that both of the proteins, USP26 and AR, could facilitate the transition of G1-G2 phase in the Leydig cells (TM3). This effect also promoted the proliferation of the Leydig cells.
The cell cycle studies performed using FCM detected that the 2 proteins, USP26 and AR, could facilitate the transition of G1-G2 phase in the Leydig cells (TM3). This effect also promoted the proliferation of the Leydig cells. Moreover, the results from co-immunoprecipitation (CO-IP), immunofluorescence and western blot assays showed that the physiological process due to USP26 interacted with AR and influenced AR deubiquitination, thus upregulating the proteins CCND1 and SPATA46 - which are associated with cell cycle progression and spermatogenesis - as well as decreasing the expression of TP73. Thus, these processes took place through the AR signaling pathway. Furthermore, the USP26 mimic plasmid transfection enhanced these activities, while, conversely, USP26 and AR inhibitor plasmid transfection suppressed the physiological events.
Taken together, the effects of AR deubiquitinated by USP26 could modulate sperm maturation and spermatogenesis through the androgen receptor signaling pathway.
蛋白质的翻译后修饰控制着细胞内各种生理和病理事件。
在这项研究中，我们通过雄激素受体（AR）信号通路研究了 X 连锁去泛素化酶 USP26 在介导 AR 去泛素化以参与精子成熟和精子发生的生理事件中的影响。
流式细胞术（FCM）检测的细胞周期结果表明，USP26 和 AR 这两种蛋白都能促进 Leydig 细胞（TM3）中 G1-G2 期的转变。这种作用也促进了 Leydig 细胞的增殖。
FCM 进行的细胞周期研究表明，USP26 和 AR 这两种蛋白都能促进 Leydig 细胞（TM3）中 G1-G2 期的转变。这种作用也促进了 Leydig 细胞的增殖。此外，免疫共沉淀（CO-IP）、免疫荧光和 Western blot 检测结果表明，USP26 与 AR 的生理过程相互作用并影响 AR 的去泛素化，从而上调与细胞周期进程和精子发生相关的蛋白 CCND1 和 SPATA46，并下调 TP73 的表达。因此，这些过程是通过 AR 信号通路发生的。此外，USP26 模拟质粒转染增强了这些活性，而 USP26 和 AR 抑制剂质粒转染则抑制了生理事件。
综上所述，USP26 去泛素化的 AR 可通过雄激素受体信号通路调节精子成熟和精子发生。
