E3 ubiquitin ligase ASB17 is required for spermiation in mice

BackgroundA major goal of spermiation is to degrade the apical ectoplasmic specialization (ES) junction between Sertoli cells and elongating spermatids in preparation for the eventual disengagement of spermatids into the lumen. E3 ubiquitin ligases mediate the process of ubiquitination and the subsequent proteasomal degradation, but their specific role during spermiation remains largely unexplored.MethodsAnkyrin repeat and SOCS box protein 17 (Asb17)-knockout mice were generated via a CRISPR/Cas9 approach. Epididymal sperm parameters were assessed by a computer-assisted sperm analysis (CASA) system, and morphological analysis of testicular tissues were performed based on histological and immunostaining staining, and transmission electron microscopy (TEM). The interactions between ASB17 and Espin (ESPN) were predicted by HawkDock server and validated through protein pull-down and immunoprecipitation assays.ResultsWe report that ASB17, an E3 ligase, is required for the completion of spermiation and that mice lacking Asb17 are oligozoospermic owing to spermiation failure. ASB17-deficient mice are fertile; however, spermatids exhibit a disorganized ES junction, resulting in retention within the seminiferous epithelium. Mechanistically, ASB17 deficiency leads to excess accumulation of ESPN, an actin-binding essential structural component of the ES. We determined that ASB17 regulates the removal of the ES through ubiquitin mediated protein degradation of ESPN.ConclusionsIn summary, our study describes a role for ASB17 in the regulation of cell-cell junctions between germ cells and somatic cells in the testis. These findings establish a novel mechanism for the regulatory role of E3 ligases during spermatogenesis.     

HECT型E3泛素连接酶在肿瘤中作用的研究现状和进展

肿瘤的发生和发展是多因素、多步骤的复杂过程。而泛素化是多步级联的蛋白质修饰过程,是维持真核细胞内稳态的重要机制。其中E3泛素连接酶家族是泛素-蛋白酶体系统的重要成分,可催化多种蛋白底物的泛素化,促进其被蛋白酶体系统降解。迄今为止,E3泛素连接酶在多种肿瘤细胞生物学过程中发挥着重要作用,包括细胞增殖、凋亡及周期调控。而HECT型E3泛素连接酶作为E3泛素连接酶最早被研究的一种,其主要参与蛋白质翻译后转录调控的泛素化修饰过程。本文就HECT型E3泛素连接酶及其在肿瘤中作用的现状和最新研究进展进行综述。