机构：[1]School of Traditional Chinese Pharmacy & State Key Laboratory of NaturalMedicines, China Pharmaceutical University, Nanjing 211198, China[2]State KeyLaboratory of Phytochemistry and Plant Resources in West China, KunmingInstitute of Botany, Chinese Academy of Sciences, Kunming 650201, China[3]State Key Laboratory of Biotherapy/Collaborative Innovation Center ofBiotherapy and Cancer Center, West China Hospital of Sichuan University,Chengdu 610041, China四川大学华西医院[4]State Key Laboratory of Cell Biology, ShanghaiInstitute of Biochemistry and Cell Biology, Chinese Academy of Sciences,Shanghai 200031, China[5]MOE Key Laboratory of Bioinformatics andBioinformatics Division, TNLIST/Department of Automation, TsinghuaUniversity, Beijing 100084, China
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.
基金：
This work was supported by the National Natural Science Foundation of China
(U1032602, 91013002, 31470428, 81225025, 81630103), the National Basic
Research Program of China (2013CB127505), the Fund of Chinese Academy of
Sciences (XDA09030301-4, Hundred Talents Program), the National New Drug
Innovation Major Project of China (2017ZX09309027), the Fund for
Introduction of High-level Talents from China Pharmaceutical University, the
Program for Jiangsu Province Innovative Research Team, the Fund Program of
State Key Laboratory of Natural Medicines (3144060028), and “111” Project
(B16046) from the Ministry of Education of China and the State Administration
of Foreign Experts Affairs of China. We thank Dr. Yin ZN (Nankai University) for
providing us with NF-κB-luciferase transgenic mice. We thank Li Y (Kunming
Institute of Botany, CAS) and Li J (Shanghai Institute of Materia Medica, CAS) for
advices.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2018]版：
大类|2 区生物
小类|2 区细胞生物学
最新[2023]版：
大类|1 区生物学
小类|2 区细胞生物学
第一作者：
第一作者机构：[1]School of Traditional Chinese Pharmacy & State Key Laboratory of NaturalMedicines, China Pharmaceutical University, Nanjing 211198, China[2]State KeyLaboratory of Phytochemistry and Plant Resources in West China, KunmingInstitute of Botany, Chinese Academy of Sciences, Kunming 650201, China
通讯作者：
通讯机构：[1]School of Traditional Chinese Pharmacy & State Key Laboratory of NaturalMedicines, China Pharmaceutical University, Nanjing 211198, China[2]State KeyLaboratory of Phytochemistry and Plant Resources in West China, KunmingInstitute of Botany, Chinese Academy of Sciences, Kunming 650201, China[4]State Key Laboratory of Cell Biology, ShanghaiInstitute of Biochemistry and Cell Biology, Chinese Academy of Sciences,Shanghai 200031, China
推荐引用方式(GB/T 7714)：
Zhe Wang,Simeng Zhao,Lihua Song,et al.Natural cyclopeptide RA-V inhibits the NF-κB signaling pathway by targeting TAK1.[J].Cell death & disease.2018,9(7):715.doi:10.1038/s41419-018-0743-2.
APA：
Zhe Wang,Simeng Zhao,Lihua Song,Yuzhi Pu,Qiang Wang...&Ninghua Tan.(2018).Natural cyclopeptide RA-V inhibits the NF-κB signaling pathway by targeting TAK1..Cell death & disease,9,(7)
MLA：
Zhe Wang,et al."Natural cyclopeptide RA-V inhibits the NF-κB signaling pathway by targeting TAK1.".Cell death & disease 9..7(2018):715
生物学