The E3 Ubiquitin Ligase CRL4 Regulates Proliferation and Progression Through Meiosis in Chinese Mitten Crab Eriocheir sinensis.
The E3 Ubiquitin Ligase CRL4 Regulates Proliferation and Progression Through Meiosis in Chinese Mitten Crab Eriocheir sinensis.
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E3 泛素连接酶 CRL4 通过减数分裂调节中华绒螯蟹的增殖和进展。
DOI：
10.1095/biolreprod.115.137661
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Wang Qun
中科院分区：
文献类型：
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作者：
Wang Yuan-Li;Li Dan;Yang Hong-Dan;He Lin;Sun Wen-Juan;Duan Ze-Lin;Wang Qun
Cullin-RING E3是由称为Cullin的支架蛋白组成的多亚基泛素连接酶，Cullin是一种调节多种细胞途径的RING指蛋白;然而，它们对雄性性腺发育的贡献，特别是中华绒螯蟹（Eriocheir sinensis）的精子发生，还不清楚。我们从E. sinensis可能参与调节雄性性腺发育。本研究的目的是确定Cullin 4对精子发生的作用机制。我们观察到Cullin 4、p53和增殖细胞核抗原在初级精母细胞中有特异性表达和定位。我们还在体外研究了NEDD 8激活酶抑制剂MLN 4924处理后Cullin底物的蓄积。细胞周期抑制剂p27和p21分别在24和36 h后显著积累。我们推测，p53介导的自发性生殖细胞凋亡作为一种质量控制机制，以消除有缺陷的生殖细胞和Cullin 4复合体维持p53，p21，和p27在初级精母细胞的稳态，以调节精子发生的E。sinensis。由于其广泛的进化保守性，Cullin 4可能在其他生物中类似地调节生殖系发育。
The Cullin-RING E3s are multisubunit ubiquitin ligases composed of a scaffold protein known as Cullin, a RING finger protein that regulates diverse cellular pathways; however, their contribution to male gonad development, especially the spermatogenesis of the Chinese mitten crab (Eriocheir sinensis), is not well understood. We identified five evolutionarily conserved Cullins from the transcriptome and genome ofE. sinensisthat are potentially involved in regulating male gonad development. The aim of the current study was to determine the mechanisms of Cullin4’s effects on spermatogenesis. We observed that Cullin4, p53, and proliferating cell nuclear antigen had a specific expression and localization in primary spermatocytes. We also investigated the accumulation of Cullin substrates by treatment with inhibitor of NEDD8-activating enzyme MLN4924 in vitro. Cell cycle inhibitors p27 and p21 accumulated significantly after 24 and 36 h, respectively. We speculated that p53-mediated spontaneous germ cell apoptosis acts as a quality control mechanism to eliminate defective germ cells and that the Cullin4 complex maintains p53, p21, and p27 homeostasis in primary spermatocytes to regulate spermatogenesis ofE. sinensis. Given its widespread evolutionary conservation, Cullin4 may regulate germ line development similarly in other organisms.