Anzola Mónica, Burgos Juan José
Departamento Z y Dinamica Celular, Facultad de Farmacia, Universidad del País Vasco, Paseo Universidades 6, 01007 Vitoria-Gasteiz, Spain.
Expert Rev Mol Med. 2003 Nov 19;5(28):1-16. doi: 10.1017/S1462399403006926.
Hepatocellular carcinoma (HCC) is the most important primary hepatic cancer and is a common cancer type worldwide. Many aetiological factors have been related to HCC development, such as liver cirrhosis, hepatitis viruses and alcohol consumption. Inactivation of the p53 tumour suppressor gene is one of the most common abnormalities in many tumours, including HCC. p53 is of crucial importance for the regulation of the cell cycle and the maintenance of genomic integrity. In HCC, hepatitis B and C virus (HBV and HCV) effect carcinogenic pathways, independently leading to anomalies in p53 function. Several authors have reported that some HCV proteins, such as the core, NS5A and NS3 proteins, interact with p53 and prevent its correct function. The mechanisms of action of these HCV proteins in relation to p53 are not completely clear, but they might cause its cytoplasmic retention or accumulation in the perinuclear region where the protein is not functional. The identification of the interactions between p53 and HCV proteins is of great importance for therapeutic strategies aimed at reducing the chronicity and/or carcinogenicity of the virus.
肝细胞癌（HCC）是最重要的原发性肝癌，也是全球常见的癌症类型。许多病因学因素都与HCC的发生发展有关，如肝硬化、肝炎病毒和饮酒等。p53肿瘤抑制基因失活是包括HCC在内的许多肿瘤中最常见的异常之一。p53对于细胞周期调控和基因组完整性的维持至关重要。在HCC中，乙型和丙型肝炎病毒（HBV和HCV）影响致癌途径，独立导致p53功能异常。几位作者报告称，一些HCV蛋白，如核心蛋白、NS5A蛋白和NS3蛋白，与p53相互作用并阻止其正常功能。这些HCV蛋白与p53相关的作用机制尚不完全清楚，但它们可能导致p53在细胞质中滞留或在核周区域积聚，而该区域的蛋白无功能。鉴定p53与HCV蛋白之间的相互作用对于旨在降低病毒慢性感染和/或致癌性的治疗策略具有重要意义。
