文献类型：期刊文献

英文题名：Veratramine modulates AP-1-dependent gene transcription by directly binding to programmable DNA

作者：Bai, Fang[1,2,3];Liu, Kangdong[4,5,6,7];Li, Huiliang[8];Wang, Jiawei[2];Zhu, Junsheng[2,7];Hao, Pei[9];Zhu, Lili[2];Zhang, Shoude[2];Shan, Lei[8];Ma, Weiya[6];Bode, Ann M.[6];Zhang, Weidong[8];Li, Honglin[2];Dong, Zigang[6,7]

机构：[1]Dalian Univ Technol, Fac Chem Environm & Biol Sci & Technol, Dalian 116023, Peoples R China;[2]East China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Sch Pharm, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[3]Rice Univ, Ctr Theoret Biol Phys, Houston, TX 77005 USA;[4]Zhengzhou Univ, Dept Pathophysiol, Basic Med Coll, 100 Sci Rd, Zhengzhou 450001, Henan, Peoples R China;[5]Collaborat Innovat Ctr Henan Prov Canc Chemopreve, Zhengzhou 450001, Henan, Peoples R China;[6]Univ Minnesota, Hormel Inst, 801 16th Ave NE, Austin, MN 55912 USA;[7]China US Henan Hormel Canc Inst, 127 Dongmin Rd, Zhengzhou 450008, Henan, Peoples R China;[8]Second Mil Med Univ, Sch Pharm, Dept Nat Prod Chem, 325 Guohe Rd, Shanghai 200433, Peoples R China;[9]Chinese Acad Sci, Inst Pasteur Shanghai, Key Lab Mol Virol & Immunol, Shanghai 200031, Peoples R China

年份：2018

卷号：46

期号：2

起止页码：546

外文期刊名：NUCLEIC ACIDS RESEARCH

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000423812300011)】；

基金：National Key Research and Development Program [2016YFA0502304 to H.L.L.]; Professor of Chang Jiang Scholars Program (to W.D.Z); National Natural Science Foundation of China [81372269 to K.D.L., 81230090, 81520108030, 21472238 to W.D.Z.]; Shanghai Engineering Research Center for the Preparation of Bioactive Natural Products [16DZ2280200 to W.D.Z.]; Special Program for Applied Research on Super Computation of the NSFC-Guangdong Joint Fund (the second phase) [U1501501]; Honglin Li is also sponsored National Program for Support of Top-notch Young Professionals. Funding for open access charge: National Key Research and Development Program [2016YFA0502304].

语种：英文

摘要：Because the transcription factor activator protein-1 (AP-1) regulates a variety of protein-encoding genes, it is a participant in many cellular functions, including proliferation, transformation, epithelial mesenchymal transition (EMT), and apoptosis. Inhibitors targeting AP-1 have potential use in the treatment of cancer and other inflammatory diseases. Here, we identify veratramine as a potent natural modulator of AP-1, which selectively binds to a specific site (TRE 5'-TGACTCA-3') of the AP-1 target DNA sequence and regulates AP-1-dependent gene transcription without interfering with cystosolic signaling cascades that might lead to AP-1 activation. Moreover, RNA-seq experiments demonstrate that veratramine does not act on the Hedgehog signaling pathway in contrast to its analogue, cyclopamine, and likely does not harbor the same teratogenicity and toxicity. Additionally, veratramine effectively suppresses EGF-induced AP-1 transactivation and transformation of JB6 P+ cells. Finally, we demonstrate that veratramine inhibits solar-ultraviolet-induced AP-1 activation in mice. The identification of veratramine and new findings in its specific regulation of AP-1 down stream genes pave ways to discovering and designing regulators to regulate transcription factor.