Department of Biochemistry, Chungnam National University College of Medicine, Daejeon 35015, Korea.
Department of Medical Science, Chungnam National University College of Medicine, Daejeon 35015, Korea.
Int J Mol Sci. 2018 Oct 3;19(10):3020. doi: 10.3390/ijms19103020.
The endoplasmic reticulum (ER) is an essential compartment of the biosynthesis, folding, assembly, and trafficking of secretory and transmembrane proteins, and consequently, eukaryotic cells possess specialized machineries to ensure that the ER enables the proteins to acquire adequate folding and maturation for maintaining protein homeostasis, a process which is termed proteostasis. However, a large variety of physiological and pathological perturbations lead to the accumulation of misfolded proteins in the ER, which is referred to as ER stress. To resolve ER stress and restore proteostasis, cells have evolutionary conserved protein quality-control machineries of the ER, consisting of the unfolded protein response (UPR) of the ER, ER-associated degradation (ERAD), and autophagy. Furthermore, protein quality-control machineries of the ER play pivotal roles in the control of differentiation, progression of cell cycle, inflammation, immunity, and aging. Therefore, severe and non-resolvable ER stress is closely associated with tumor development, aggressiveness, and response to therapies for cancer. In this review, we highlight current knowledge in the molecular understanding and physiological relevance of protein quality control of the ER and discuss new insights into how protein quality control of the ER is implicated in the pathogenesis of cancer, which could contribute to therapeutic intervention in cancer.
内质网（ER）是生物合成、折叠、组装和转运分泌蛋白和跨膜蛋白的必需区室，因此，真核细胞拥有专门的机制来确保内质网使蛋白质获得足够的折叠和成熟，以维持蛋白质的内稳态，这一过程被称为蛋白质稳态。然而，大量的生理和病理扰动导致错误折叠的蛋白质在内质网中积累，这被称为内质网应激。为了解决内质网应激并恢复蛋白质稳态，细胞具有进化保守的内质网蛋白质质量控制机制，包括内质网未折叠蛋白反应（UPR）、内质网相关降解（ERAD）和自噬。此外，内质网蛋白质质量控制机制在分化、细胞周期进展、炎症、免疫和衰老的控制中发挥着关键作用。因此，严重且无法解决的内质网应激与肿瘤的发生、侵袭性和对癌症治疗的反应密切相关。在这篇综述中，我们强调了内质网蛋白质质量控制的分子理解和生理相关性的最新知识，并讨论了内质网蛋白质质量控制如何与癌症的发病机制有关的新见解，这可能有助于癌症的治疗干预。
