摘要
蛋白质泛素化是真核生物细胞内蛋白质合成后最重要和最普遍的修饰方式之一。发生在蛋白质底物上的泛素化,由于其泛素化方式及形成泛素链的连接形式的多样性,又统称为泛素信号途径。研究表明,泛素信号途径对蛋白质的调节作用分为降解相关和非相关的两种。细胞内蛋白质的降解主要通过泛素-蛋白酶体或溶酶体-自噬途径来完成。一般认为,通过泛素-蛋白酶体降解的蛋白质具有很强的选择性,而通过溶酶体-自噬途径降解的蛋白质一般选择性较差。然而,近年来,细胞自噬受体如p62等的发现则表明细胞自噬同样具有很强的选择性,这一类由细胞自噬受体介导的细胞自噬被称为细胞选择性自噬(Selective autophagy)。蛋白质泛素化及降解调控几乎所有类型的细胞活动;与之对应的是,蛋白质泛素化及降解异常与包括肿瘤在内的多种人类疾病的发生发展密切相关。本文综述了泛素信号途径调控蛋白质通过蛋白酶体或自噬途径降解的基本过程和部分最新进展,并结合本实验室的研究成果介绍泛素化修饰细胞自噬受体调控细胞选择性自噬的新机制。
In eukaryotes, protein ubiquitylation （or ubiquitination） is ubiquitous and one of the most important post-translational modifications. Due to the diversity in the way that ubiquitin is conjugated on protein substrate and the configuration in which ubiquitin chains might be formed, the mechanisms through which cellular activities are regulated by protein ubiquitylation are collectively termed as ubiquitin signaling. The functional consequence of protein ubiquitylation could be classified into two categories： proteolytic or non-proteolytic. In the cell, all proteins are pre-destined for degradation mainly through the ubiquitinroteasome system （UPS） or the lysosome-dependent autophagy pathway. Protein degradation through UPS was once believed to be more selective and delicate than autophagy. However, this notion was overturned by the discovery of auto- phagy receptors such as p62 that selectively recognize and target cargos to lysosome and degradation through autophagy. The process was termed as slective autophagy. So far, ubiquitin signaling and proteolysis are known to regulate almost all aspects of celllular activities. Accordingly, their aberrance are closely associated with or feature multiple human disorders including tumor. Here we review the general understanding of how ubiquitn signaling might regulate protein degradation through UPS or autophagy, with an emphasis on latest development in the crosstalk between ubiqutin signaling and selective autophagy.
出处
《生命的化学》
CAS
CSCD
2015年第2期144-155,共12页
Chemistry of Life
基金
科技部重大研究计划(2012CB910800
2013CB910900)
关键词
泛素化
选择性自噬
细胞自噬受体
Ubiquitylation
selective autophagy
cellular autophagy receptor
