去泛素化酶与干细胞特性调控

Deubiquitinases and Stem Cell Identity Regulation

胚胎干细胞(embryonic stem cells,ESCs)和诱导多能干细胞(induced pluripotent stem cells,iPSCs)是能够进行自我更新和多系分化的细胞系,几乎所有的干细胞都具有这两大特性。干细胞的这种特性受到各类因素的控制和调节,如基因表达调控层面的转录因子调节、RNA层面的可变剪接、蛋白质翻译后修饰以及蛋白质在机体内代谢调控等。其中,蛋白质翻译后修饰(post translational modifications,PTMs)机制之一泛素蛋白酶体系统在调节干细胞自我更新、增殖和分化中起着核心作用。该文综述了泛素动态变化在干细胞自我更新和分化调节中的重要作用,泛素连接酶和去泛素化酶作为泛素蛋白酶体系统中研究最为深入和广泛的酶分子,对于维持干细胞自我更新和分化的蛋白分子稳态有重要作用。该文将重点对去泛素化酶的作用进行总结和归纳,以充分揭示泛素动态调控对干细胞自我更新和分化的贡献。

ESCs(embryonic stem cells)and iPSCs(induced pluripotent stem cells)are the class of cell lines capable of self-renewal and multi-lineage differentiation.Almost all stem cells possess these two characteristics.This characteristic of stem cells is controlled and regulated by many factors,such as transcription factor regulation at the level of gene expression,mRNA alternative splicing regulation,protein post-translational modification,etc.Given UPS(ubiquitin proteasome system),which is a major machinery as a part of the protein post-translational modifications,has played great roles in the regulation of protein dynamics.There is no doubt UPS plays a key role in regulating the self-renewal,reproduction and differentiation of stem cells.Among the three kinds of enzymes contained in the UPS,the E3 ligases and deubiquitinases are the most researched and highly focused.Here this study concluded the important cellular roles of ubiquitin dynamics in the regulating of stem cell characteristics,focusing on the summary and induction of the role of DUBs(deubiquitinates)in the control of stem cell fate to fully uncover the contribution of ubiquitin dynamics to stem cell self-renewal and differentiation.