Identification of sumoylated targets in proliferating mouse spermatogonia and human testicular seminomas.
Identification of sumoylated targets in proliferating mouse spermatogonia and human testicular seminomas.
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DOI：
10.4103/aja.aja_11_20
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发表时间：
2020-11
影响因子：
2.9
通讯作者：
Levy R
中科院分区：
文献类型：
--
作者：
Vigodner M;Lucas B;Kemeny S;Schwartz T;Levy R
精子发生受复杂的翻译后修饰网络的调节。 Sumoylation（小泛素样修饰剂或SUMO蛋白的修饰）被确定为不同细胞类型中的重要细胞事件。 Sumo蛋白在睾丸中高度表达，它们在精子发生中的作用已经开始阐明。鉴于Sumoylation在其他组织中有丝分裂和癌症进展中的重要作用，本研究的目的是鉴定Sumo的靶标在增殖的小鼠精子症和人类学瘤组织中，并最初检查与组织增殖活性相关的Sumoylation水平。使用新鲜纯化的精子症和C18-4精子细胞系，质谱分析确定了与精子症增殖有关的几个SUMO靶标（例如热休克蛋白60 [HSP60]和前蛋白）。组织阵列和蛋白质印迹方法表明，Sumo表达是人类学瘤的重要特征，并且肿瘤组织的增殖活性与Sumo表达水平呈正相关。用Si-RNA的Sumoylation下调不足以显着影响C18-4精子的增殖。但是，相扑过表达增加了细胞的增殖率。这些数据表明细胞对相扑水平升高更敏感，并且这种情况可能导致细胞增殖和癌症的上调。质谱分析在精子瘤样品中鉴定出一百个相扑靶标。值得注意的是，许多已鉴定的蛋白质（例如增殖的细胞核抗原[PCNA]，DNA拓扑异构酶2-α[TOP2A]，禁止蛋白，14-3-3蛋白等）都与致癌转化和癌症进展有关。
Spermatogenesis is regulated by a complex network of posttranslation modifications. Sumoylation (a modification by small ubiquitin-like modifiers, or SUMO proteins) was identified as an important cellular event in different cell types. SUMO proteins are highly expressed in the testis, and their role during spermatogenesis has begun to be elucidated. Given the important role of sumoylation in the regulation of mitosis and cancer progression in other tissues, the aim of the current study was to identify the targets of SUMO in proliferating mouse spermatogonia and human seminoma tissues and to initially examine the level of sumoylation in relation to the proliferative activity of the tissues. Using freshly purified spermatogonia and C18-4 spermatogonia cell line, mass spectrometry analysis identified several SUMO targets implicated into the proliferation of spermatogonia (such as heat shock protein 60 [HSP60] and prohibitin). Tissue array and western blot approaches showed that SUMO expression is a prominent feature of human seminomas and that the proliferative activity of the tumor tissues was positively correlated with the level of SUMO expression. Downregulation of sumoylation with si-RNA was not sufficient to significantly affect the proliferation of C18-4 spermatogonia; however, SUMO overexpression increased the proliferation rate of the cells. These data suggest that cells are more sensitive to an elevated level of SUMO, and that this situation may lead to an upregulated cellular proliferation and, possibly, cancer. Mass spectrometry analysis identified around a hundred SUMO targets in seminoma samples. Notably, many of the identified proteins (such as proliferating cell nuclear antigen [PCNA], DNA topoisomerase 2-alpha [Top2A], prohibitin, 14-3-3 protein, and others) were implicated in oncogenic transformation and cancer progression.
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