Microbial Regulation of p53 Tumor Suppressor.
Microbial Regulation of p53 Tumor Suppressor.
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DOI：
10.1371/journal.ppat.1005099
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发表时间：
2015-09
期刊：
影响因子：
6.7
通讯作者：
Peek RM
中科院分区：
文献类型：
--
作者：
Zaika AI;Wei J;Noto JM;Peek RM
p53肿瘤抑制因子被鉴定为与由猴空泡病毒40（SV 40）产生的大T抗原相互作用的蛋白质。随后对SV 40和其他肿瘤病毒抑制p53的研究不仅有助于更好地了解病毒生物学，而且还塑造了我们对人类肿瘤发生的认识。然而，最近的研究发现，p53的抑制并不严格限于病毒。一些细菌病原体还主动抑制p53蛋白并诱导其降解，导致细胞应激反应的改变。这种现象最初是在感染幽门螺杆菌的胃上皮细胞中发现的，幽门螺杆菌是一种常见的感染人类胃的细菌病原体，与胃癌密切相关。除了H. pylori，最近发现许多其他细菌物种抑制p53。这些发现为宿主-细菌相互作用和与细菌感染相关的肿瘤发生提供了新的见解。本文综述了宿主-细菌相互作用的一个新方面：细菌病原体和保护宿主免受癌症发展的肿瘤抑制机制之间的直接相互作用。近年来的研究表明，多种病原菌均能有效抑制p53蛋白介导的肿瘤抑制途径，而p53蛋白在调节多种细胞应激反应和预防肿瘤发生中起着关键作用。p53的细菌降解首先在幽门螺杆菌感染的背景下被发现，幽门螺杆菌感染是目前已知的胃腺癌最强的风险因素。然而，这种现象并不限于H。幽门螺杆菌和许多其它细菌病原体利用各种机制抑制p53。细菌对p53的抑制与细菌调节宿主细胞对DNA损伤、代谢应激和潜在的其他应激源的反应有关。这是一个充满活力的研究领域，将继续发展，并为更好地了解宿主-微生物相互作用和肿瘤发生做出重要贡献。这些研究可能为药物开发提供新的分子靶点和机会。
p53 tumor suppressor has been identified as a protein interacting with the large T antigen produced by simian vacuolating virus 40 (SV40). Subsequent research on p53 inhibition by SV40 and other tumor viruses has not only helped to gain a better understanding of viral biology, but also shaped our knowledge of human tumorigenesis. Recent studies have found, however, that inhibition of p53 is not strictly in the realm of viruses. Some bacterial pathogens also actively inhibit p53 protein and induce its degradation, resulting in alteration of cellular stress responses. This phenomenon was initially characterized in gastric epithelial cells infected with Helicobacter pylori, a bacterial pathogen that commonly infects the human stomach and is strongly linked to gastric cancer. Besides H. pylori, a number of other bacterial species were recently discovered to inhibit p53. These findings provide novel insights into host–bacteria interactions and tumorigenesis associated with bacterial infections. This review focuses on a novel aspect of host–bacteria interactions: the direct interplay between bacterial pathogens and tumor suppression mechanisms that protect the host from cancer development. Recent studies revealed that various pathogenic bacteria actively inhibit the major tumor suppression pathway mediated by p53 protein that plays a key role in the regulation of multiple cellular stress responses and prevention of cancerogenesis. Bacterial degradation of p53 was first discovered in the context of Helicobacter pylori infection, which is currently the strongest known risk factor for adenocarcinoma of the stomach. This phenomenon, however, is not limited to H. pylori, and many other bacterial pathogens inhibit p53 using various mechanisms. Inhibition of p53 by bacteria is linked to bacterial modulation of the host cellular responses to DNA damage, metabolic stress, and, potentially, other stressors. This is a dynamic area of research that will continue to evolve and make important contributions to a better understanding of host–microbe interactions and tumorigenesis. These studies may offer new molecular targets and opportunities for drug development.