Bhaduri Satarupa, Scott Nicola A, Neal Sonya E
School of Biological Sciences, the Section of Cell and Developmental Biology, University of California San Diego, La Jolla, California 92093, USA.
Cold Spring Harb Perspect Biol. 2023 Feb 1;15(2):a041248. doi: 10.1101/cshperspect.a041248.
The endoplasmic reticulum (ER) is an essential organelle in eukaryotic cells and is a major site for protein folding, modification, and lipid synthesis. Perturbations within the ER, such as protein misfolding and high demand for protein folding, lead to dysregulation of the ER protein quality control network and ER stress. Recently, the rhomboid superfamily has emerged as a critical player in ER protein quality control because it has diverse cellular functions, including ER-associated degradation (ERAD), endosome Golgi-associated degradation (EGAD), and ER preemptive quality control (ERpQC). This breadth of function both illustrates the importance of the rhomboid superfamily in health and diseases and emphasizes the necessity of understanding their mechanisms of action. Because dysregulation of rhomboid proteins has been implicated in various diseases, such as neurological disorders and cancers, they represent promising potential therapeutic drug targets. This review provides a comprehensive account of the various roles of rhomboid proteins in the context of ER protein quality control and discusses their significance in health and disease.
内质网（ER）是真核细胞中的一种重要细胞器，是蛋白质折叠、修饰和脂质合成的主要场所。内质网内的紊乱，如蛋白质错误折叠和对蛋白质折叠的高需求，会导致内质网蛋白质质量控制网络失调和内质网应激。最近，类菱形蛋白酶超家族已成为内质网蛋白质质量控制中的关键角色，因为它具有多种细胞功能，包括内质网相关降解（ERAD）、内体-高尔基体相关降解（EGAD）和内质网抢先质量控制（ERpQC）。这种广泛的功能既说明了类菱形蛋白酶超家族在健康和疾病中的重要性，也强调了了解其作用机制的必要性。由于类菱形蛋白酶的失调与各种疾病有关，如神经疾病和癌症，它们是很有前景的潜在治疗药物靶点。本综述全面阐述了类菱形蛋白酶在ER蛋白质质量控制背景下的各种作用，并讨论了它们在健康和疾病中的意义。
