AGO2 phosphorylation by c-Src kinase promotes tumorigenesis
| Autor: | Ran Chen, Zhi Yang, Hailong Zhang, Yanli Wang, Shengfang Ge, Jianxiu Yu, Tianqi Liu, Jiayu Fang, Jian Huang, Xian Zhao |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Cancer Research PTMs post-translational modifications c-Src AGO2 GST glutathione S-transferase Tyrosine phosphorylation Mice chemistry.chemical_compound 0302 clinical medicine Neoplasms RISC RNA-induced silencing complex Phosphorylation Tyrosine biology Chemistry Kinase Y tyr tyrosine Tryptophan AGO2 Argonaute-2 IP immunoprecipitation lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Cell biology Saracatinib Cell Transformation Neoplastic src-Family Kinases 030220 oncology & carcinogenesis Argonaute Proteins RNA Interference Disease Susceptibility Tyrosine kinase Protein Binding Signal Transduction Original article RISC complex Models Biological lcsh:RC254-282 P4H prolyl-4-hydroxylase Cell Line 03 medical and health sciences miRNAs microRNAs Animals Humans Protein Kinase Inhibitors Binding Sites EGFR epidermal growth factor receptor MicroRNAs 030104 developmental biology Tumorigenesis biology.protein Ectopic expression F phenylalanine Dicer |
| Zdroj: | Neoplasia: An International Journal for Oncology Research, Vol 22, Iss 3, Pp 129-141 (2020) Neoplasia (New York, N.Y.) |
| ISSN: | 1476-5586 |
| Popis: | Numerous studies have reported that c-Src is highly expressed with high tyrosine kinase activity in a variety of tumors. However, it remains unclear whether c-Src contributes to the miRNA pathway. Here, we report that c-Src can interact with and phosphorylate AGO2, a core component of RISC complex, at tyr 393, tyr 529 and tyr749. Mechanistically, it is confirmed that c-Src phosphorylation of AGO2 at tyr393 reduces its binding to DICER, thereby suppressing the maturation of long-loop pre-miR-192. However, the other two phosphorylation sites don’t work on this function. Significantly, Ectopic expression of wild-type AGO2, but not the three tyrosine site mutants, has an obvious tumor-promoting effect in vitro and in vivo, which function could be blocked thoroughly by treatment with c-Src kinase inhibitor, Saracatinib. Our findings identify AGO2 as c-Src target and c-Src phosphorylation of AGO2 may therefore play a potential role during tumor progress. Keywords: c-Src, AGO2, Tyrosine phosphorylation, Tumorigenesis, Saracatinib |
| Databáze: | OpenAIRE |
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