Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
DNA Repair (Amst). 2019 Jan;73:110-119. doi: 10.1016/j.dnarep.2018.11.008. Epub 2018 Nov 20.
Maintenance of genome integrity and stability is a critical responsibility of the DNA damage response (DDR) within cells, such that any disruption in this kinase-based signaling pathway leads to development of various disorders, particularly cancer. The tumor suppressor P53-binding protein 1 (53BP1), as one of the main mediators of DDR, plays a pivotal role in orchestrating the choice of double-strand break (DSB) repair pathway and contains interaction surfaces for numerous DSB-responsive proteins. It has been extensively demonstrated that aberrant expression of 53BP1 contributes to tumor occurrence and development. 53BP1 loss of function in tumor tissues is also related to tumor progression and poor prognosis in human malignancies. Due to undeniable importance of this protein in various aspects of cancer initiation/progression, angiogenesis, metastasis and development of drug resistance, as well as its targeting in the treatment of cancer, this review focused on explaining the structure and function of 53BP1 and its contribution to cancer.
维持基因组完整性和稳定性是细胞内 DNA 损伤反应 (DDR) 的一项关键职责,因此,这种基于激酶的信号通路的任何中断都会导致各种疾病的发展,特别是癌症。肿瘤抑制因子 P53 结合蛋白 1(53BP1)作为 DDR 的主要介质之一,在协调双链断裂 (DSB) 修复途径的选择方面发挥着关键作用,并包含许多 DSB 反应蛋白的相互作用表面。已经广泛证明,53BP1 的异常表达有助于肿瘤的发生和发展。肿瘤组织中 53BP1 功能丧失也与人类恶性肿瘤的肿瘤进展和预后不良有关。由于该蛋白在癌症发生/进展、血管生成、转移和耐药性发展以及癌症治疗中的靶向作用方面具有不可否认的重要性,因此本综述重点解释了 53BP1 的结构和功能及其对癌症的贡献。