泛素化是最常见的翻译后修饰方式，对于各种细胞调控过程至关重要。RNF187，也称为RING结构域AP1辅激活因子1，是RING指环家族的成员之一。RNF187能够促进各种肿瘤细胞的增殖和迁移。然而，其在调控精原细胞中是否具有类似作用尚不清楚。本研究探讨了RNF187在小鼠精原细胞系（GC-1）中的作用和分子机制。我们发现，RNF187的沉默抑制了GC-1细胞的增殖和迁移，并促进了细胞的凋亡。RNF187的过表达显著增加了GC-1细胞的增殖和迁移。此外，我们通过共免疫沉淀和质谱分析确定了角蛋白36/角蛋白84（KRT36/KRT84）与RNF187之间的相互作用。RNF187通过赖氨酸48连接多泛素化降解KRT36/KRT84来促进GC-1细胞的生长。随后，我们发现KRT36或KRT84的过表达显著减弱了RNF187过表达GC-1细胞的增殖和迁移。总之，我们的研究探讨了RNF187通过赖氨酸48连接多泛素化介导的KRT36/KRT84降解在调控精原细胞生长中的作用。这可能为治疗因异常精原细胞发育导致的不育提供了一种有前景的新策略。 ©2023年作者。由Wiley Periodicals LLC代表美国实验生物学联合会出版发表的《FASEB Journal》

Ubiquitination is the most common post-translational modification and is essential for various cellular regulatory processes. RNF187, which is known as RING domain AP1 coactivator-1, is a member of the RING finger family. RNF187 can promote the proliferation and migration of various tumor cells. However, whether it has a similar role in regulating spermatogonia is not clear. This study explored the role and molecular mechanism of RNF187 in a mouse spermatogonia cell line (GC-1). We found that RNF187 knockdown reduced the proliferation and migration of GC-1 cells and promoted their apoptosis. RNF187 overexpression significantly increased the proliferation and migration of GC-1 cells. In addition, we identified Keratin36/Keratin84 (KRT36/KRT84) as interactors with RNF187 by co-immunoprecipitation and mass spectrometry analyses. RNF187 promoted GC-1 cell growth by degrading KRT36/KRT84 via lysine 48-linked polyubiquitination. Subsequently, we found that KRT36 or KRT84 overexpression significantly attenuated proliferation and migration of RNF187-overexpressing GC-1 cells. In summary, our study explored the involvement of RNF187 in regulating the growth of spermatogonia via lysine 48-linked polyubiquitination-mediated degradation of KRT36/KRT84. This may provide a promising new strategy for treating infertility caused by abnormal spermatogonia development.© 2023 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.