Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.
BMB Rep. 2020 Jan;53(1):56-63. doi: 10.5483/BMBRep.2020.53.1.283.
The ubiquitin-proteasome system (UPS) and autophagy are two major degradative pathways of proteins in eukaryotic cells. As about 30% of newly synthesized proteins are known to be misfolded under normal cell conditions, the precise and timely operation of the UPS and autophagy to remove them as well as their tightly controlled regulation, is so important for proper cell function and survival. In the UPS, target proteins are labeled by small proteins called ubiquitin, which are then transported to the proteasome complex for degradation. Alternatively, many greatly damaged proteins are believed to be delivered to the lysosome for autophagic degradation. Although these autophagy and UPS pathways have not been considered to be directly related, many recent studies proposed their close link and dynamic interconversion. In this review, we'll focus on the several regulatory molecules that function in both UPS and autophagy and their crosstalk. Among the proposed multiple modulators, we will take a closer look at the so-called main connector of UPS-autophagy regulation, p62. Last, the functional role of p62 in the mitophagy and its implication for the pathogenesis of Parkinson's disease, one of the major neurodegenerative diseases, will be briefly reviewed. [BMB Reports 2020; 53(1): 56-63].
泛素-蛋白酶体系统（UPS）和自噬是真核细胞中两种主要的蛋白质降解途径。由于大约 30%的新合成蛋白质在正常细胞条件下被认为是错误折叠的，因此 UPS 和自噬的精确和及时运作来清除这些蛋白质以及它们的严格控制调节，对于细胞的正常功能和存活非常重要。在 UPS 中，靶蛋白被称为泛素的小蛋白标记，然后被运送到蛋白酶体复合物进行降解。或者，许多严重受损的蛋白质被认为被递送到溶酶体进行自噬降解。尽管这些自噬和 UPS 途径尚未被认为是直接相关的，但许多最近的研究提出了它们的密切联系和动态转换。在这篇综述中，我们将重点介绍在 UPS 和自噬中起作用的几种调节分子及其相互作用。在提出的多种调节剂中，我们将仔细研究所谓的 UPS-自噬调节的主要连接器 p62。最后，将简要回顾 p62 在 mitophagy 中的功能作用及其对帕金森病等主要神经退行性疾病之一的发病机制的影响。[BMB 报告 2020；53(1):56-63]。
