Ubiquitin Ligase Huwe1 Modulates Spermatogenesis by Regulating Spermatogonial Differentiation and Entry into Meiosis.
Ubiquitin Ligase Huwe1 Modulates Spermatogenesis by Regulating Spermatogonial Differentiation and Entry into Meiosis.
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泛素连接酶 Huwe1 通过调节精原细胞分化和进入减数分裂来调节精子发生。
DOI：
10.1038/s41598-017-17902-0
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发表时间：
2017-12-19
影响因子：
4.6
通讯作者：
Wing SS
中科院分区：
文献类型：
--
作者：
Bose R;Sheng K;Moawad AR;Manku G;O'Flaherty C;Taketo T;Culty M;Fok KL;Wing SS
精子发生包括一系列高度调控的过程，包括有丝分裂增殖、减数分裂和细胞重塑。虽然基因表达的改变是众所周知的调节精子发生，转录后机制是不太清楚。泛素蛋白酶体系统在蛋白质周转中起重要作用，并可能参与这些转录后机制。我们先前在睾丸中鉴定了泛素连接酶Huwe1，并表明它可以泛素化组蛋白。由于组蛋白的调节在精子发生的许多步骤中都很重要，因此我们通过检查Huwe1在分化的精原细胞、精母细胞和精子细胞中失活的影响，对Huwe1在这一过程中的功能进行了完整的表征。Huwe1在精原细胞分化中的失活导致精原细胞的消耗和形成较少的前细线期精母细胞。细胞变性与DNA损伤反应蛋白γH2AX的积累、下游信号传导受损和凋亡有关。Huwe1在精母细胞中的失活表明Huwe1不是减数分裂和精子发生所必需的，但可导致γH2AX的积累。总的来说，这些结果提供了一个全面的调查Huwe1在精子发生中的功能，并揭示Huwe1的关键作用，作为一个调制器的DNA损伤反应途径在精原细胞分化的最早阶段。
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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影响因子：
30.5
作者：
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影响因子：
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DOI：
10.1073/pnas.94.26.14602
发表时间：
1997-12-23
影响因子：
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作者：
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通讯作者：
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