Ubiquitin Ligase Huwe1 Modulates Spermatogenesis by Regulating Spermatogonial Differentiation and Entry into Meiosis
Publication in refereed journal

香港中文大學研究人員
替代計量分析
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其它資訊
摘要Spermatogenesis consists of a series of highly regulated processes that include mitotic proliferation, meiosis and cellular remodeling. Although alterations in gene expression are well known to modulate spermatogenesis, posttranscriptional mechanisms are less well defined. The ubiquitin proteasome system plays a significant role in protein turnover and may be involved in these posttranscriptional mechanisms. We previously identified ubiquitin ligase Huwe1 in the testis and showed that it can ubiquitinate histones. Since modulation of histones is important at many steps in spermatogenesis, we performed a complete characterization of the functions of Huwe1 in this process by examining the effects of its inactivation in the differentiating spermatogonia, spermatocytes and spermatids. Inactivation of Huwe1 in differentiating spermatogonia led to their depletion and formation of fewer pre-leptotene spermatocytes. The cell degeneration was associated with an accumulation of DNA damage response protein γH2AX, impaired downstream signalling and apoptosis. Inactivation of Huwe1 in spermatocytes indicated that Huwe1 is not essential for meiosis and spermiogenesis, but can result in accumulation of γH2AX. Collectively, these results provide a comprehensive survey of the functions of Huwe1 in spermatogenesis and reveal Huwe1’s critical role as a modulator of the DNA damage response pathway in the earliest steps of spermatogonial differentiation.
著者Rohini BOSE, Kai SHENG, Adel R. MOAWARD, Gurpreet MANKU, Cristian O’FLAHERTY, Teruko TAKETO, Martine CULTY, Kin Lam FOK, Simon S. WING
期刊名稱Scientific Reports
出版年份2017
月份12
日期19
卷號7
出版社NATURE PUBLISHING GROUP
頁次17759
國際標準期刊號2045-2322
電子國際標準期刊號2045-2322
語言英式英語
Web of Science 學科類別Multidisciplinary Sciences;Science & Technology - Other Topics

上次更新時間 2021-19-01 於 01:34