Student Research Committee, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran; Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Life Sci. 2022 Jul 15;301:120620. doi: 10.1016/j.lfs.2022.120620. Epub 2022 May 6.
In tumor cells, the endoplasmic reticulum (ER) plays an essential role in maintaining cellular proteostasis by stimulating unfolded protein response (UPR) underlying stress conditions. ER-associated degradation (ERAD) is a critical pathway of the UPR to protect cells from ER stress-induced apoptosis and the elimination of unfolded or misfolded proteins by the ubiquitin-proteasome system (UPS). 3-Hydroxy-3-methylglutaryl reductase degradation (HRD1) as an E3 ubiquitin ligase plays an essential role in the ubiquitination and dislocation of misfolded protein in ERAD. In addition, HRD1 can target other normal folded proteins. In various types of cancer, the expression of HRD1 is dysregulated, and it targets different molecules to develop cancer hallmarks or suppress the progression of the disease. Recent investigations have defined the role of HRD1 in drug resistance in types of cancer. This review focuses on the molecular mechanisms of HRD1 and its roles in cancer pathogenesis and discusses the worthiness of targeting HRD1 as a novel therapeutic strategy in cancer.
在肿瘤细胞中，内质网（ER）通过刺激未折叠蛋白反应（UPR）在应激条件下发挥着维持细胞蛋白稳态的重要作用。ER 相关降解（ERAD）是 UPR 的一个关键途径，可保护细胞免受 ER 应激诱导的细胞凋亡和通过泛素-蛋白酶体系统（UPS）消除未折叠或错误折叠的蛋白质。3-羟基-3-甲基戊二酰基辅酶 A 还原酶降解（HRD1）作为一种 E3 泛素连接酶，在 ERAD 中未折叠蛋白的泛素化和易位中发挥着重要作用。此外，HRD1 还可以靶向其他正常折叠的蛋白质。在各种类型的癌症中，HRD1 的表达失调，它靶向不同的分子来发展癌症特征或抑制疾病的进展。最近的研究已经确定了 HRD1 在多种癌症耐药中的作用。本综述重点介绍了 HRD1 的分子机制及其在癌症发病机制中的作用，并讨论了将 HRD1 作为癌症治疗的新策略的价值。
