| 杨益言,王卫东.p53动力学:从细胞命运到炎症免疫[J].中华放射医学与防护杂志,2024,44(12):1090-1094.Yang Yiyan,Wang Weidong.p53 dynamics: from determining cell fate to inflammation and immune regulation[J].Chin J Radiol Med Prot,2024,44(12):1090-1094 |
| p53动力学:从细胞命运到炎症免疫 |
| p53 dynamics: from determining cell fate to inflammation and immune regulation |
| 投稿时间：2024-04-08 |
| DOI：10.3760/cma.j.cn112271-20240408-00121 |
| 中文关键词: p53 动力学 细胞命运 炎症 免疫 |
| 英文关键词:p53 Dynamics Cell fate Inflammation Immunity |
| 基金项目:四川省自然科学基金重点项目(2022NSFSC0051) |
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| 中文摘要: |
| 自1979年p53 发现以来,其角色和功能不断变化,从最初的癌基因、抑癌基因,50%的肿瘤突变率,到细胞周期调控、基因组稳定性、细胞凋亡、老化,以及最近的炎症和免疫调控等。作为细胞应激反应的信息处理中心,p53动力学不仅编码应激的种类和强度,同时调控多种下游基因,决定了细胞命运的走向,且与组织的辐射敏感性密切相关;其动力学机制主要在于启动以MDM2为代表的多个反馈环路。p53不仅直接参与机体cGAS-TING等固有免疫反应和T、B细胞为主的适应性免疫,也与多种炎症反应有关;其突变体为肿瘤免疫提供新抗原。p53抑癌靶向治疗迄今未获临床成功,其免疫调控的新策略或许会带来人类抗癌的曙光。 |
| 英文摘要: |
| Since p53 was discovered in 1979, the understanding of its roles and functions has continuously changed. Initially, p53 was known as a cancer gene and tumor suppressor gene, with a 50% mutation rate in tumors. Then, p53 was found to be involved in cell cycle regulation, genomic stability, apoptosis, and cell aging. More recently, it has been discovered that p53 plays a role in inflammation and immune regulation. As the information processing center of cellular stress responses, p53 dynamics not only encode the types and intensity of stress but also regulate multiple downstream genes, determining the fate of cells and closely related to the radiosensitivity of tissues. The primary mechanism behind p53 dynamics is to initiate multiple feedback loops represented by MDM2. Specifically, p53 is not only directly involved in innate immune responses such as cGAS-TING and adaptive immune responses dominated by T and B cells but also associated with various inflammatory responses. Its mutants provide new antigens for tumor immunity. Although targeted therapy against p53 in cancer has not yet been clinically successful, the new strategies for immune regulation using p53 may provide a new chance of cancer therapy for human beings. |
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