Natural cyclopeptide RA-V inhibits the NF-κB signaling pathway by targeting TAK1.
Zhe WangSimeng ZhaoLihua SongYuzhi PuQiang WangGuangzhi ZengXing LiuMing BaiShao LiFabao GaoLijuan ChenChen WangNing-Hua TanPublished in: Cell death & disease (2018)
Rubiaceae-type cyclopeptides (RAs) are a type of plant cyclopeptides from the Rubia that have garnered significant attention owing to their unique bicyclic structures and amazing antitumour activities. Our recent work has shown that RAs suppress inflammation and angiogenesis and induce apoptosis. However, the underlying mechanism and targets remained unknown. Nuclear factor κB (NF-κB) signaling pathway plays a critical role in these biological processes, prompting us to investigate whether and how RAs affect this pathway. By screening compound libraries using NF-κB-dependent luciferase reporter, we observed that RA-V is the best NF-κB inhibitor. Further experiments demonstrated that RA-V interrupted the TAK1-TAB2 interaction and targeted TAK1 in this pathway. Moreover, RA-V prevented endotoxin shock and inhibited NF-κB activation and tumor growth in vivo. These findings clarify the mechanism of RA-V on NF-κB pathway and might account for the majority of known bioactivities of RA-V, which will help RA-V develop as new antiinflammatory and antitumour therapies.
Keyphrases
- signaling pathway
- nuclear factor
- pi k akt
- rheumatoid arthritis
- oxidative stress
- lps induced
- disease activity
- toll like receptor
- induced apoptosis
- cell cycle arrest
- ankylosing spondylitis
- epithelial mesenchymal transition
- interstitial lung disease
- cell proliferation
- working memory
- inflammatory response
- endothelial cells
- crispr cas
- immune response
- systemic sclerosis
- mass spectrometry