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Ubiquitin Ligase Huwe1 Modulates Spermatogenesis by Regulating Spermatogonial Differentiation and Entry into Meiosis

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 s...

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Autores principales: Bose, Rohini, Sheng, Kai, Moawad, Adel R., Manku, Gurpreet, O’Flaherty, Cristian, Taketo, Teruko, Culty, Martine, Fok, Kin Lam, Wing, Simon S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5736635/
https://www.ncbi.nlm.nih.gov/pubmed/29259204
http://dx.doi.org/10.1038/s41598-017-17902-0
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author Bose, Rohini
Sheng, Kai
Moawad, Adel R.
Manku, Gurpreet
O’Flaherty, Cristian
Taketo, Teruko
Culty, Martine
Fok, Kin Lam
Wing, Simon S.
author_facet Bose, Rohini
Sheng, Kai
Moawad, Adel R.
Manku, Gurpreet
O’Flaherty, Cristian
Taketo, Teruko
Culty, Martine
Fok, Kin Lam
Wing, Simon S.
author_sort Bose, Rohini
collection PubMed
description 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.
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spelling pubmed-57366352017-12-21 Ubiquitin Ligase Huwe1 Modulates Spermatogenesis by Regulating Spermatogonial Differentiation and Entry into Meiosis Bose, Rohini Sheng, Kai Moawad, Adel R. Manku, Gurpreet O’Flaherty, Cristian Taketo, Teruko Culty, Martine Fok, Kin Lam Wing, Simon S. Sci Rep Article 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. Nature Publishing Group UK 2017-12-19 /pmc/articles/PMC5736635/ /pubmed/29259204 http://dx.doi.org/10.1038/s41598-017-17902-0 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Bose, Rohini
Sheng, Kai
Moawad, Adel R.
Manku, Gurpreet
O’Flaherty, Cristian
Taketo, Teruko
Culty, Martine
Fok, Kin Lam
Wing, Simon S.
Ubiquitin Ligase Huwe1 Modulates Spermatogenesis by Regulating Spermatogonial Differentiation and Entry into Meiosis
title Ubiquitin Ligase Huwe1 Modulates Spermatogenesis by Regulating Spermatogonial Differentiation and Entry into Meiosis
title_full Ubiquitin Ligase Huwe1 Modulates Spermatogenesis by Regulating Spermatogonial Differentiation and Entry into Meiosis
title_fullStr Ubiquitin Ligase Huwe1 Modulates Spermatogenesis by Regulating Spermatogonial Differentiation and Entry into Meiosis
title_full_unstemmed Ubiquitin Ligase Huwe1 Modulates Spermatogenesis by Regulating Spermatogonial Differentiation and Entry into Meiosis
title_short Ubiquitin Ligase Huwe1 Modulates Spermatogenesis by Regulating Spermatogonial Differentiation and Entry into Meiosis
title_sort ubiquitin ligase huwe1 modulates spermatogenesis by regulating spermatogonial differentiation and entry into meiosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5736635/
https://www.ncbi.nlm.nih.gov/pubmed/29259204
http://dx.doi.org/10.1038/s41598-017-17902-0
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