Ambiguous Role of p53 in Transcription-Dependent Tumor Cell Death

Romanova, Angelina A.; Grigoreva, Tatyana A.; Zenina, Anastasia D.; Smirnaya, Anna D.; Margolina, Kira Y.; Sagaidak, Aleksandra; Tribulovich, Vyacheslav G.

doi:10.3390/ijms27020769

Open AccessReview

Ambiguous Role of p53 in Transcription-Dependent Tumor Cell Death

by

Angelina A. Romanova

,

Tatyana A. Grigoreva

^*

,

Anastasia D. Zenina

,

Anna D. Smirnaya

,

Kira Y. Margolina

,

Aleksandra Sagaidak

and

Vyacheslav G. Tribulovich

^*

Laboratory of Molecular Pharmacology, St. Petersburg State Institute of Technology (Technical University), St. Petersburg 190013, Russia

^*

Authors to whom correspondence should be addressed.

Int. J. Mol. Sci. 2026, 27(2), 769; https://doi.org/10.3390/ijms27020769

Submission received: 4 December 2025 / Revised: 27 December 2025 / Accepted: 29 December 2025 / Published: 12 January 2026

(This article belongs to the Special Issue Oncogenes and Tumor Suppressors: From Basic Science to Therapeutic Applications)

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Abstract

Currently, research in anti-cancer therapy remains a priority. This is driven by two main challenges: the difficulty of modeling and developing targeted or precision drugs and the multiple, often unpredictable, body responses to treatment. The primary objective of modern anti-cancer drugs is the induction of cancer cell death. One of the key regulators of cell death is the tumor suppressor protein p53. This protein is a well-known transcription factor encoded by TP53. Despite the fact that p53 is generally considered a pro-apoptotic inducer, it also regulates cell death pathways such as necrosis and autophagy. Given the diversity of p53-mediated cell death pathways, establishing a specific activated mechanism is a necessary step in developing effective anti-cancer drugs, since certain types of cell death can cause adverse outcomes in patients, including infection, sepsis, tumor progression and metastasis. The review summarizes knowledge about p53-dependent cell death mechanisms and the p53 transcriptional targets that are involved. It also describes shared molecular pathways among apoptosis, necrosis, and autophagy, as well as the methods and markers used to distinguish one type of cell death from another.

Keywords: p53; cell death; apoptosis; necrosis; autophagy

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MDPI and ACS Style

Romanova, A.A.; Grigoreva, T.A.; Zenina, A.D.; Smirnaya, A.D.; Margolina, K.Y.; Sagaidak, A.; Tribulovich, V.G. Ambiguous Role of p53 in Transcription-Dependent Tumor Cell Death. Int. J. Mol. Sci. 2026, 27, 769. https://doi.org/10.3390/ijms27020769

AMA Style

Romanova AA, Grigoreva TA, Zenina AD, Smirnaya AD, Margolina KY, Sagaidak A, Tribulovich VG. Ambiguous Role of p53 in Transcription-Dependent Tumor Cell Death. International Journal of Molecular Sciences. 2026; 27(2):769. https://doi.org/10.3390/ijms27020769

Chicago/Turabian Style

Romanova, Angelina A., Tatyana A. Grigoreva, Anastasia D. Zenina, Anna D. Smirnaya, Kira Y. Margolina, Aleksandra Sagaidak, and Vyacheslav G. Tribulovich. 2026. "Ambiguous Role of p53 in Transcription-Dependent Tumor Cell Death" International Journal of Molecular Sciences 27, no. 2: 769. https://doi.org/10.3390/ijms27020769

APA Style

Romanova, A. A., Grigoreva, T. A., Zenina, A. D., Smirnaya, A. D., Margolina, K. Y., Sagaidak, A., & Tribulovich, V. G. (2026). Ambiguous Role of p53 in Transcription-Dependent Tumor Cell Death. International Journal of Molecular Sciences, 27(2), 769. https://doi.org/10.3390/ijms27020769

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

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Ambiguous Role of p53 in Transcription-Dependent Tumor Cell Death

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