Synthetic lethality of combined ULK1 defection and p53 restoration induce pyroptosis by directly upregulating GSDME transcription and cleavage activation through ROS/NLRP3 signaling

• Published in: Journal of experimental & clinical cancer research Vol. 43; no. 1; pp. 248 - 20
• Main Authors: Chen, Wei, Yang, Kai-Bin, Zhang, Yuan-Zhe, Lin, Zai-Shan, Chen, Jin-Wei, Qi, Si-Fan, Wu, Chen-Fei, Feng, Gong-Kan, Yang, Da-Jun, Chen, Ming, Zhu, Xiao-Feng, Li, Xuan
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 30.08.2024; BioMed Central; BMC
• Subjects: Animals; Antibodies; Autophagy-Related Protein-1 Homolog - genetics; Autophagy-Related Protein-1 Homolog - metabolism; Cancer; Cell culture; Cell cycle; Cell death; Cell Line, Tumor; Cloning; CRISPR; DNA methylation; Enzyme-linked immunosorbent assay; Enzymes; Ethylenediaminetetraacetic acid; Female; Genes; Genetic aspects; Genetic transcription; Health aspects; Humans; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Kinases; Ligases; MDM2 inhibitor; Mice; Mitophagy; NLR Family, Pyrin Domain-Containing 3 Protein; Penicillin; Plasmids; Proteins; Pyroptosis; Reactive oxygen species; Reactive Oxygen Species - metabolism; Signal Transduction; Synthetic Lethal Mutations; TP53; Tumor proteins; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Tumors; Ubiquitin; ULK1; Up-Regulation; Grand Island; United States > US; Reactive oxygen species; ULK1; Pyroptosis; Mitophagy; TP53; MDM2 inhibitor

High expression of ubiquitin ligase MDM2 is a primary cause of p53 inactivation in many tumors, making it a promising therapeutic target. However, MDM2 inhibitors have failed in clinical trials due to p53-induced feedback that enhances MDM2 expression. This underscores the urgent need to find an eff...