دورية أكاديمية
Carboxypeptidase A4 negatively regulates HGS-ETR1/2-induced pyroptosis by forming a positive feedback loop with the AKT signalling pathway
| العنوان: | Carboxypeptidase A4 negatively regulates HGS-ETR1/2-induced pyroptosis by forming a positive feedback loop with the AKT signalling pathway |
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| المؤلفون: | Luoling Wang, Rilin Deng, Shuishun Chen, Renyun Tian, Mengmeng Guo, Zihao Chen, Yingdan Zhang, Huiyi Li, Qian Liu, Songqing Tang, Haizhen Zhu |
| المصدر: | Cell Death and Disease, Vol 14, Iss 12, Pp 1-13 (2023) |
| بيانات النشر: | Nature Publishing Group, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Cytology |
| مصطلحات موضوعية: | Cytology, QH573-671 |
| الوصف: | Abstract Pyroptosis, a mode of inflammatory cell death, has recently gained significant attention. However, the underlying mechanism remains poorly understood. HGS-ETR1/2 is a humanized monoclonal antibody that can bind to DR4/5 on the cell membrane and induce cell apoptosis by activating the death receptor signalling pathway. In this study, by using morphological observation, fluorescence double staining, LDH release and immunoblot detection, we confirmed for the first time that HGS-ETR1/2 can induce GSDME-mediated pyroptosis in hepatocellular carcinoma cells. Our study found that both inhibition of the AKT signalling pathway and silencing of CPA4 promote pyroptosis, while the overexpression of CPA4 inhibits it. Furthermore, we identified a positive regulatory feedback loop is formed between CPA4 and AKT phosphorylation. Specifically, CPA4 modulates AKT phosphorylation by regulating the expression of the AKT phosphatase PP2A, while inhibition of the AKT signalling pathway leads to a decreased transcription and translation levels of CPA4. Our study reveals a novel mechanism of pyroptosis induced by HGS-ETR1/2, which may provide a crucial foundation for future investigations into cancer immunotherapy. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2041-4889 |
| Relation: | https://doaj.org/toc/2041-4889 |
| DOI: | 10.1038/s41419-023-06327-5 |
| URL الوصول: | https://doaj.org/article/552dec21a87b49dbbb3ee4330ed4c0ab |
| رقم الأكسشن: | edsdoj.552dec21a87b49dbbb3ee4330ed4c0ab |
| قاعدة البيانات: | Directory of Open Access Journals |
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