Synthetic lethality of combined ULK1 defection and p53 restoration induce pyroptosis by directly upregulating GSDME transcription and cleavage activation through ROS/NLRP3 signaling
Our research demonstrates that ULK1 deficiency can synergize with MDM2 inhibitors to induce pyroptosis. p53 plays a direct role in activating GSDME transcription, while ULK1 deficiency triggers upregulation of the ROS-NLRP3 signaling pathway, leading to GSDME cleavage and activation. These findings underscore the pivotal role of p53 in determining pyroptosis and provide new avenues for the clinical application of p53 restoration therapies, as well as suggesting potential combination strategies.
Authors
- Yuan-Zhe Zhang (ORCID: https://orcid.org/0000-0002-4027-4271)
- Kai‐Bin Yang
- Wei Chen (ORCID: https://orcid.org/0000-0003-2275-4527)
- Xuan Li (ORCID: https://orcid.org/0000-0001-5744-5818)
- Ming Chen (ORCID: https://orcid.org/0000-0001-9869-4036)
- Jinwei Chen (ORCID: https://orcid.org/0000-0001-9439-0297)
- Gong‐Kan Feng
- Xiaofeng Zhu (ORCID: https://orcid.org/0009-0000-1745-2271)
- Si-Fan Qi
- Da-Jun Yang
- Zai-Shan Lin
- Chen‐Fei Wu
Institutions
- Sun Yat-sen University (CN)
- Key Laboratory of Guangdong Province (CN)
- Sun Yat-sen University Cancer Center (CN)
- State Key Laboratory of Oncology in South China
Publication Details
- Journal
- Journal of Experimental & Clinical Cancer Research
- Published
- 2024-08-30
- DOI
- https://doi.org/10.1186/s13046-024-03168-8
- Citations
- 28
- Primary Topic
- Inflammasome and immune disorders
- Type
- article
- Field-Weighted Citation Impact
- 6.55