2025-07-07
p53 Regulation of Non-Apoptotic Cell Death: Research Advances and Therapeutic Potential
p53, a critical transcription factor, regulates not only apoptosis but also non-apoptotic cell death (NACD) pathways, including ferroptosis, necroptosis, pyroptosis, autophagy-dependent cell death, and parthanatos. Research reveals that p53 modulates ferroptosis by downregulating SLC7A11 and activating ALOX12, showing promise in tumor suppression, particularly in triple-negative breast cancer. Necroptosis and pyroptosis, linked to inflammation, involve p53 regulation of RIPK1/3 and CASP1/11. Autophagy-dependent cell death is driven by p53 through Beclin 1 and TP53INP1, while entotic cell death and parthanatos are associated with genomic stability and DNA damage repair. Targeting p53-regulated NACD offers new therapeutic avenues for cancer, organ damage, and immune disorders.
