泛素蛋白酶体途径及其在体外受精中的作用研究进展

摘要

泛素蛋白酶体途径(ubiquitin proteasome pathway,UPP)是生物体内最主要的蛋白质降解途径,与多种疾病有关,在生物体内具有十分重要的作用,主要降解错误折叠的、多余的蛋白质.UPP是一个循环途径,其主要作用起始于泛素(ubiquitin,Ub)的激活,是受泛素激活酶(ubiquitin-activating enzyme,E1,酵母菌中是UbE1)、泛素结合酶(ubiquitin-conjugating enzyme,E2,UbE2)、泛素连接酶(ubiquitin-protein ligase,E3,UbE3)和去泛素化酶(deubiquitinating enzymes,DUBs)调控的级联过程,最终使被多聚泛素化(polyubiquitination,polyubiquitination,PolyUb)标记的蛋白底物在UPP的蛋白水解核心——26S蛋白酶体内被降解成寡肽,寡肽可以进入新的蛋白循环,Ub则由DUBs去除进入下一个UPP循环.UPP在海鞘类和一些哺乳类体外受精(in vitro fertilization,IVF)过程中具有十分重要的作用,能够参与精子获能和顶体反应(acrosomal reaction,AR),促进精子顶体胞吐,在精卵结合时降解透明带(zona pellucida,ZP)蛋白,辅助精子穿透卵母细胞ZP,促进精子与卵母细胞ZP的融合,从而促使IVF的成功.通过在IVF液中添加一些UPP相关的抗体或抑制剂能够抑制IVF过程中的多精人卵,提高IVF率.作者综述了UPP的主要组成成分及其对IVF的辅助作用及相关抗体的研究进展,以期为今后研究UPP循环在生物体内的作用机制、与生物体内各种疾病的关系、在IVF过程中的作用机制及抑制多精人卵等提供一定的理论依据.%The ubiquitin proteasome pathway (UPP) is the most important pathway for protein degradation in the organism,and UPP is also related with many diseases,it plays a very important role in the organism which mainly degrade misfolded proteins.UPP is a circular pathway,its main function begins with the activation of ubiquitin(Ub),and the process is a cascade process that regulated by the ubiquitin activating enzyme (E1,in yeast is UbE1),ubiquitin conjugating enzyme (E2,UbE2),ubiquitin ligase enzyme (E3,UbE3) and deubiquitinating enzymes(DUBs).Eventually make the protein substrate that labeled by polyubiquitination degrad into oligopeptides in UPP protein hydrolysis core 26S proteasome.The oligopeptides can be reused by organisms,and the Ub was removed by DUBs for the next UPP cycle.And the studies have shown that UPP plays an important role in ascidians and some mammalian in vitro fertilization (IVF) process,it can participate in sperm capacitation and acrosome reaction(AR),promote sperm acrosome exocytosis,degrade zona pellucida (ZP) protein in the process of sperm-oocyte binding,help sperm penetrate oocytes ZP,promote the fusion of sperm and oocytes ZP,so to promote the success of the IVF.And by adding some UPP related antibody or inhibitors in the IVF solution can inhibit polyspermy in the process of IVF,to improve the IVF rates.The authors mainly describes the main components of UPP and its auxiliary functions for IVF,and the research progress of the related antibody.This review may provide some theoretical basis for the future research of the mechanism of UPP cycle in organism,the relationships with various diseases in the organism,the mechanism in IVF process and the inhibition of polyspermy.