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Veratramine modulates AP-1-dependent gene transcription by directly binding to programmable DNA | |
2018 | |
发表期刊 | NUCLEIC ACIDS RESEARCH |
ISSN | 0305-1048 |
EISSN | 1362-4962 |
卷号 | 46期号:2页码:546-557 |
发表状态 | 已发表 |
DOI | 10.1093/nar/gkx1241 |
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. |
URL | 查看原文 |
收录类别 | SCI |
WOS研究方向 | Biochemistry & Molecular Biology |
WOS类目 | Biochemistry & Molecular Biology |
WOS记录号 | WOS:000423812300011 |
WOS关键词 | HEDGEHOG-SIGNALING PATHWAY ; NF-KAPPA-B ; ACTIVATOR PROTEIN-1 ; C-FOS ; AP-1 ; CANCER ; PROMOTER ; CELLS ; TRANSFORMATION ; INFLAMMATION |
原始文献类型 | Article |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/120093 |
专题 | 个人在本单位外知识产出 |
共同第一作者 | Liu, Kangdong; Li, Huiliang |
通讯作者 | Zhang, Weidong; Li, Honglin; Dong, Zigang |
作者单位 | 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 |
推荐引用方式 GB/T 7714 | Bai, Fang,Liu, Kangdong,Li, Huiliang,et al. Veratramine modulates AP-1-dependent gene transcription by directly binding to programmable DNA[J]. NUCLEIC ACIDS RESEARCH,2018,46(2):546-557. |
APA | Bai, Fang.,Liu, Kangdong.,Li, Huiliang.,Wang, Jiawei.,Zhu, Junsheng.,...&Dong, Zigang.(2018).Veratramine modulates AP-1-dependent gene transcription by directly binding to programmable DNA.NUCLEIC ACIDS RESEARCH,46(2),546-557. |
MLA | Bai, Fang,et al."Veratramine modulates AP-1-dependent gene transcription by directly binding to programmable DNA".NUCLEIC ACIDS RESEARCH 46.2(2018):546-557. |
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