Kocaturk Nur Mehpare, Gozuacik Devrim
Molecular Biology, Genetics and Bioengineering Program, Faculty of Engineering and Natural Sciences, Sabanci University, Istanbul, Turkey.
Center of Excellence for Functional Surfaces and Interfaces for Nano Diagnostics (EFSUN), Sabanci University, Istanbul, Turkey.
Front Cell Dev Biol. 2018 Oct 2;6:128. doi: 10.3389/fcell.2018.00128. eCollection 2018.
Autophagy and the ubiquitin-proteasome system (UPS) are the two major intracellular quality control and recycling mechanisms that are responsible for cellular homeostasis in eukaryotes. Ubiquitylation is utilized as a degradation signal by both systems, yet, different mechanisms are in play. The UPS is responsible for the degradation of short-lived proteins and soluble misfolded proteins whereas autophagy eliminates long-lived proteins, insoluble protein aggregates and even whole organelles (e.g., mitochondria, peroxisomes) and intracellular parasites (e.g., bacteria). Both the UPS and selective autophagy recognize their targets through their ubiquitin tags. In addition to an indirect connection between the two systems through ubiquitylated proteins, recent data indicate the presence of connections and reciprocal regulation mechanisms between these degradation pathways. In this review, we summarize these direct and indirect interactions and crosstalks between autophagy and the UPS, and their implications for cellular stress responses and homeostasis.
自噬和泛素-蛋白酶体系统（UPS）是真核生物中负责细胞内稳态的两种主要的细胞内质量控制和再循环机制。两种系统都利用泛素化作为降解信号，但发挥作用的机制不同。UPS负责降解短命蛋白和可溶性错误折叠蛋白，而自噬则清除长命蛋白、不溶性蛋白聚集体，甚至整个细胞器（如线粒体、过氧化物酶体）和细胞内寄生虫（如细菌）。UPS和选择性自噬都通过其泛素标签识别各自的靶标。除了通过泛素化蛋白在两个系统之间存在间接联系外，最近的数据表明这些降解途径之间存在联系和相互调节机制。在本综述中，我们总结了自噬与UPS之间的这些直接和间接相互作用及串扰，以及它们对细胞应激反应和体内平衡的影响。
