Understanding the complexity of p53 in a new era of tumor suppression
了解肿瘤抑制新时代 p53 的复杂性
- PMID: 38729160
- PMCID: PMC11190820
- DOI: 10.1016/j.ccell.2024.04.009
Understanding the complexity of p53 in a new era of tumor suppression
了解肿瘤抑制新时代 p53 的复杂性
Abstract 抽象
p53 was discovered 45 years ago as an SV40 large T antigen binding protein, coded by the most frequently mutated TP53 gene in human cancers. As a transcription factor, p53 is tightly regulated by a rich network of post-translational modifications to execute its diverse functions in tumor suppression. Although early studies established p53-mediated cell-cycle arrest, apoptosis, and senescence as the classic barriers in cancer development, a growing number of new functions of p53 have been discovered and the scope of p53-mediated anti-tumor activity is largely expanded. Here, we review the complexity of different layers of p53 regulation, and the recent advance of the p53 pathway in metabolism, ferroptosis, immunity, and others that contribute to tumor suppression. We also discuss the challenge regarding how to activate p53 function specifically effective in inhibiting tumor growth without harming normal homeostasis for cancer therapy.
p53 于 45 年前被发现为一种 SV40 大 T 抗原结合蛋白,由人类癌症中最常突变的 TP53 基因编码。作为一种转录因子,p53 受到丰富的翻译后修饰网络的严格调控,以在肿瘤抑制中执行其多种功能。尽管早期研究确定 p53 介导的细胞周期停滞、凋亡和衰老是癌症发展的典型障碍,但已经发现了越来越多的 p53 新功能,并且 p53 介导的抗肿瘤活性的范围在很大程度上扩大了。在这里,我们回顾了 p53 调节不同层次的复杂性,以及 p53 通路在代谢、铁死亡、免疫和其他有助于肿瘤抑制的途径方面的最新进展。我们还讨论了如何激活 p53 功能的挑战,该功能特别有效地抑制肿瘤生长,而不会损害癌症治疗的正常稳态。
Keywords:
MDM2; MDMX; apoptosis; cancer treatment; cell competition; cell-cycle arrest; ferroptosis; genome stability; immunity; metabolism; metastasis; p53; p53 mutation; p63; p73; senescence; stem cell dynamics; targeting p53; tumor suppression.
关键字:
MDM2;MDMX 的;细胞凋亡;癌症治疗;细胞竞争;细胞周期停滞;铁死亡;基因组稳定性;免疫;新陈代谢;转移;第 53 页;p53 突变;第 63 页;第 73 页;衰老;干细胞动力学;靶向 p53;肿瘤抑制。
Copyright © 2024 Elsevier Inc. All rights reserved.
版权所有 © 2024 Elsevier Inc.保留所有权利。
Conflict of interest statement
利益冲突声明
Declaration of interests O.T. is currently an employee of AstraZeneca and has stock ownership in AstraZeneca.
利益声明 O.T. 目前是阿斯利康的员工,并拥有阿斯利康的股票。
Figures 数字
Similar articles 相关文章
-
A Balancing Act: p53 Activity from Tumor Suppression to Pathology and Therapeutic Implications.
平衡行为:从肿瘤抑制到病理学和治疗意义的 p53 活性。Annu Rev Pathol. 2022 Jan 24;17:205-226. doi: 10.1146/annurev-pathol-042320-025840. Epub 2021 Oct 26. Annu Rev Pathol. 2022. PMID: 34699262 Review. -
Deciphering the acetylation code of p53 in transcription regulation and tumor suppression.
破译转录调控和肿瘤抑制中 p53 的乙酰化密码。Oncogene. 2022 May;41(22):3039-3050. doi: 10.1038/s41388-022-02331-9. Epub 2022 Apr 29. Oncogene. 2022. PMID: 35487975 Free PMC article. Review. -
The Regulation of Ferroptosis by Tumor Suppressor p53 and its Pathway.
肿瘤抑制因子 p53 对铁死亡的调节及其通路。Int J Mol Sci. 2020 Nov 9;21(21):8387. doi: 10.3390/ijms21218387. Int J Mol Sci. 2020. PMID: 33182266 Free PMC article. Review. -
Elucidating the chain of command: our current understanding of critical target genes for p53-mediated tumor suppression.
阐明指挥链:我们目前对 p53 介导的肿瘤抑制的关键靶基因的理解。Crit Rev Biochem Mol Biol. 2024 Feb-Apr;59(1-2):128-138. doi: 10.1080/10409238.2024.2344465. Epub 2024 Apr 25. Crit Rev Biochem Mol Biol. 2024. PMID: 38661126 Review. -
Unravelling mechanisms of p53-mediated tumour suppression.
揭示 p53 介导的肿瘤抑制机制。Nat Rev Cancer. 2014 May;14(5):359-70. doi: 10.1038/nrc3711. Epub 2014 Apr 17. Nat Rev Cancer. 2014. PMID: 24739573 Free PMC article.
Cited by 施引文献
-
Re-appraising the evidence for the source, regulation and function of p53-family isoforms.
重新评估 p53 家族亚型的来源、调节和功能的证据。Nucleic Acids Res. 2024 Nov 11;52(20):12112-12129. doi: 10.1093/nar/gkae855. Nucleic Acids Res. 2024. PMID: 39404067 Free PMC article. Review. -
Chronic obesity does not alter cancer survival in Tp53 R270H/+ mice.
慢性肥胖不会改变 Tp53R270H/+ 小鼠的癌症生存率。bioRxiv [Preprint]. 2024 Oct 16:2024.10.14.618190. doi: 10.1101/2024.10.14.618190. bioRxiv. 2024. PMID: 39463991 Free PMC article. Preprint. -
Transcriptomic analysis reveals transcription factors implicated in radon-induced lung carcinogenesis.
转录组学分析揭示了与 Radon 诱导的肺癌发生有关的转录因子。Toxicol Res (Camb). 2024 Oct 3;13(5):tfae161. doi: 10.1093/toxres/tfae161. eCollection 2024 Oct. Toxicol Res (Camb). 2024. PMID: 39371682 -
Ferroptosis-related oxaliplatin resistance in multiple cancers: Potential roles and therapeutic Implications.
多种癌症中与铁死亡相关的奥沙利铂耐药:潜在作用和治疗意义。Heliyon. 2024 Sep 7;10(18):e37613. doi: 10.1016/j.heliyon.2024.e37613. eCollection 2024 Sep 30. Heliyon. 2024. PMID: 39309838 Free PMC article. Review. -
Genetic Variants in p53 Pathway Genes Affect Survival of Patients with HBV-Related Hepatocellular Carcinoma.
p53 通路基因的遗传变异影响 HBV 相关肝细胞癌患者的生存。J Hepatocell Carcinoma. 2024 Aug 12;11:1541-1555. doi: 10.2147/JHC.S459792. eCollection 2024. J Hepatocell Carcinoma. 2024. PMID: 39156673 Free PMC article.
References 引用
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous