Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
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Advances in Clinical and Experimental Medicine

2020, vol. 29, nr 10, October, p. 1153–1160

doi: 10.17219/acem/123355

Publication type: original article

Language: English

License: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

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USP26 deubiquitinates androgen receptor (AR) in the maintenance of sperm maturation and spermatogenesis through the androgen receptor signaling pathway

Jing Wang1,A, Xia Zhao1,B, Renyun Hong1,C, Jing Wang1,D,E,F

1 Department of Reproductive Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China

Abstract

Background. The post-translational modifications of proteins control various physiological and pathological events in cells.
Objectives. 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.
Material and Methods. 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.
Results. 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.
Conclusion. Taken together, the effects of AR deubiquitinated by USP26 could modulate sperm maturation and spermatogenesis through the androgen receptor signaling pathway.

Key words

deubiquitination, sperm maturation, USP26

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