Multiple roles of p53 in cancer development: Regulation of tumor microenvironment, m6A modification and diverse cell death mechanisms

Wang, Xiangyu; Yang, Jianhua; Yang, Wanting; Sheng, Haiyang; Jia, Buyun; Cheng, Peng; Xu, Shanshan; Hong, Xinhui; Jiang, Chuanwei; Yang, Yinfeng; Wu, Ziyin; Wang, Jinghui

doi:10.1016/j.jare.2024.10.026

Journal of Advanced Research

2024

DOI: 10.1016/j.jare.2024.10.026

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Multiple roles of p53 in cancer development: Regulation of tumor microenvironment, m6A modification and diverse cell death mechanisms

Xiangyu Wang,

Jianhua Yang,

Wanting Yang

et al.

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Unraveling the Guardian: p53’s Multifaceted Role in the DNA Damage Response and Tumor Treatment Strategies

Zhang,

Xu,

Long

et al. 2024

IJMS

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DNA damage can lead to mutations that can alter the function of oncogenes or tumor suppressor genes, thus promoting the development of cancer. p53 plays a multifaceted and complex role in the DNA damage response and cancer progression and is known as the ‘guardian of the gene’. When DNA damage occurs, p53 is activated through a series of post-translational modifications, which stabilize the protein and enhance its function as a transcription factor. It regulates processes including cell cycle checkpoints, DNA repair and apoptosis, thereby preventing the spread of damaged DNA and maintaining genome integrity. On the one hand, p53 can initiate cell cycle arrest and induce cells to enter the G1/S and G2/M checkpoints, preventing cells with damaged DNA from continuing to proliferate and gaining time for DNA repair. At the same time, p53 can promote the activation of DNA repair pathways, including base excision repair, nucleotide excision repair and other repair pathways, to ensure the integrity of genetic material. If the damage is too severe to repair, p53 will trigger the apoptosis process to eliminate potential cancer risks in time. p53 also plays a pivotal role in cancer progression. Mutations in the p53 gene are frequently found in many cancers, and the mutated p53 not only loses its normal tumor suppressor function but may even acquire pro-cancer activity. Therefore, we also discuss therapeutic strategies targeting the p53 pathway, such as the use of small-molecule drugs to restore the function of wild-type p53, the inhibition of negative regulatory factors and synthetic lethality approaches for p53-deficient tumors. This review therefore highlights the important role of p53 in maintaining genomic stability and its potential in therapeutic strategies for cancer.

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Unraveling the Guardian: p53’s Multifaceted Role in the DNA Damage Response and Tumor Treatment Strategies

Zhang,

Xu,

Long

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

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Multiple roles of p53 in cancer development: Regulation of tumor microenvironment, m6A modification and diverse cell death mechanisms

Cited by 1 publication

References 182 publications

Unraveling the Guardian: p53’s Multifaceted Role in the DNA Damage Response and Tumor Treatment Strategies

Unraveling the Guardian: p53’s Multifaceted Role in the DNA Damage Response and Tumor Treatment Strategies

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