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Tumor necrosis factor receptor-associated factor 2 (TRAF2) is a central signaling adaptor that integrates multiple oncogenic pathways and represents potential target for cancer therapy. In this study, leveraging the extensive protein-protein interaction network of TRAF2, 100 "undruggable" key tumor-associated proteins were selected to screen for TRAF2 interactors. It was found that cytokine receptor-like factor 2 (CRLF2) is a novel interacting protein of TRAF2, and the liquidambaric acid (LDA), which can directly target TRAF2, can inhibit the TRAF2/CRLF2 interaction. Binding site studies revealed that CRLF2 binds to the TRAF domain of TRAF2 and can be blocked by LDA. Functional studies of CRLF2 indicated that TRAF2 is a key protein in the CRLF2-STAT3 (signal transducer and activator of transcription 3) signaling pathway, and LDA can regulate CRLF2-related STAT3 phosphorylation. In summary, this study reveals the TRAF2-mediated tumor protein interaction network and elucidates a new mechanism by which LDA exerts antitumor effects by inhibiting TRAF2/CRLF2 interaction to regulate the STAT3 signaling pathway. It also provides new theoretical guidance and potential strategies for the development of anti-tumor drugs targeting undruggable targets.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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