| Autor: |
Yangyang Zhang, Rui Kong, Wenbo Yang, Keyi Hu, Zhongjie Zhao, Le Li, Xinglong Geng, Liwei Liu, Hongze Chen, Peng Xiao, Danxi Liu, Yan Luo, Hua Chen, Jisheng Hu, Bei Sun |
| Rok vydání: |
2023 |
| DOI: |
10.21203/rs.3.rs-2560744/v1 |
| Popis: |
Pancreatic cancer is a malignant tumor of the digestive tract with poor prognosis. Dual-specificity phosphatase 2 (DUSP2) is a member of the mitogen-activated protein kinase phosphatase family that is involved in multiple pathophysiological processes. However, its role in pancreatic cancer remains further investigation. The most prominent feature of pancreatic cancer is its hypoxic microenvironment, which plays an important role in tumor progression, drug resistance, and immune evasion. Therefore, we explored the role of DUSP2 by simulating such tumor microenvironment and found that DUSP2 regulated the apoptosis of pancreatic cancer in vitro and in vivo. Mechanistically, DUSP2 competed with AKT1 for binding with casein kinase 2 alpha 1 (CSNK2A1) to inhibit the phosphorylation of AKT1, which played a crucial role in regulating apoptosis. Interestingly, aberrant activation of AKT1 resulted in an increase in the ubiquitin E3 ligase tripartite motif containing 21 (TRIM21), which could bind to and mediate ubiquitination-dependent proteasomal degradation of DUSP2. Taken together, our findings demonstrate a novel signal axis of CSNK2A1/AKT1 in DUSP2 regulating apoptosis and the existence of AKT1/TRIM21 feedback regulation in the degradation of DUSP2 protein in pancreatic cancer for the first time. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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