p53-Regulated non-apoptotic cell death pathways and their relevance in cancer and other diseases Review


Authors: Liu, Y.; Stockwell, B. R.; Jiang, X.; Gu, W.
Review Title: p53-Regulated non-apoptotic cell death pathways and their relevance in cancer and other diseases
Abstract: Programmed cell death is a mechanism that is crucial for numerous physiological and pathological processes. Whereas p53-mediated apoptosis is a major cell death pathway in cancer, accumulating evidence indicates that p53 also has crucial roles in controlling different non-apoptotic cell death (NACD) pathways, including ferroptosis, necroptosis, pyroptosis, autophagy-dependent cell death, entotic cell death, parthanatos and paraptosis, and may regulate PANoptosis, cuproptosis and disulfidptosis. Notably, the function of p53 in these NACDs substantially contributes to its biological effects, particularly in cancer development and other pathological processes. In this Review, we discuss recent advances in understanding the roles and underlying mechanisms of p53-mediated NACDs, focusing on ferroptosis, necroptosis and pyroptosis. We discuss the complex and distinct physiological settings in which NACDs are regulated by p53, and potential targeting of p53-regulated NACDs for the treatment of cancer and other human diseases. Finally, we highlight several important questions concerning p53-regulated NACDs that warrant further investigation. © Springer Nature Limited 2025.
Keywords: review; nonhuman; cell death; apoptosis; protein p53; pharmacology; pyroptosis; ferroptosis; autophagic cell death; necroptosis; human; disulfidptosis; paraptosis; parthanatos
Journal Title: Nature Reviews Molecular Cell Biology
Volume: 26
ISSN: 1471-0072
Publisher: Nature Publishing Group  
Publication status: Published
Date Published: 2025-08-01
Start Page: 600
End Page: 614
Language: English
DOI: 10.1038/s41580-025-00842-3
PROVIDER: scopus
PUBMED: 40204927
DOI/URL:
Notes: The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Source: Scopus
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
  1. Xuejun Jiang
    124 Jiang