Inhibiting MYC binding to the E-box DNA motif by ME47 decreases tumour xenograft growth

Lustig L. C.; Dingar D.; Tu W. B.Lourenco C.Kalkat M.Inamoto I.Ponzielli R.Chan W. C. W.Shin J. A.Penn L. Z.

首页> 外文期刊>Oncogene >Inhibiting MYC binding to the E-box DNA motif by ME47 decreases tumour xenograft growth

【24h】

Inhibiting MYC binding to the E-box DNA motif by ME47 decreases tumour xenograft growth

机译：ME47 抑制 MYC 与 E-box DNA 基序的结合可降低肿瘤异种移植物的生长

获取原文

获取原文并翻译 | 示例

掌桥外文数据库（机构版） >>

开具论文收录证明 >>

文献代查 >>

页面导航

摘要
著录项
相似文献
相关主题

摘要

Developing therapeutics to effectively inhibit the MYC oncoprotein would mark a key advance towards cancer patient care as MYC is deregulated in over 50 of human cancers. MYC deregulation is correlated with aggressive disease and poor patient outcome. Despite strong evidence in mouse models that inhibiting MYC would significantly impact tumour cell growth and patient survival, traditional approaches have not yet yielded the urgently needed therapeutic agents that directly target MYC. MYC functions through its interaction with MAX to regulate gene transcription by binding to E-box DNA response elements of MYC target genes. Here we used a structure-based strategy to design ME47, a small minimalist hybrid protein (MHP) able to disrupt the MAX: E-box interaction/binding and block transcriptional MYC activity. We show that inducing ME47 expression in established tumour xenografts inhibits tumour growth and decreases cellular proliferation. Mechanistically, we show by chromatin immunoprecipitation that ME47 binds to E-box binding sites of MYC target genes. Moreover, ME47 occupancy decreases MYC: DNA interaction at its cognate E-box binding sites. Taken together, ME47 is a prototypic MHP inhibitor that antagonizes tumour cell growth in vitro and in vivo and inhibits the interaction of MYC with DNA E-box elements. These results support ME47's role as a MYC inhibitor and suggest that MHPs provide an alternative therapeutic targeting system that can be used to target transcription factors important in human diseases, including cancer.

著录项

来源
《Oncogene》 |2017年第49期|6830-6837|共8页
作者
Lustig L. C.; Dingar D.; Tu W. B.Lourenco C.Kalkat M.Inamoto I.Ponzielli R.Chan W. C. W.Shin J. A.Penn L. Z.;
展开▼
作者单位

Univ Hlth Network, Princess Margaret Canc Ctr, Princess Margaret Canc Res Tower 13-706, Toronto, ON;

Univ Toronto, Dept Chem, Toronto, ON, Canada;

Univ Toronto, Inst Biomat & Biomed Engn, Donnelly Ctr Cellular & Biomol Res, Dept Mat Sci & Engn;

展开▼
收录信息
原文格式 PDF
正文语种英语
中图分类肿瘤学;
关键词

相似文献

外文文献
中文文献
专利

1. Numerical simulation of inhibiting effects on solid tumour cells in anti-angiogenic therapy: application of coupled mathematical model of angiogenesis with tumour growth [J] . Yan CAI, Jie WU, Shi-xiong XU, 应用数学和力学（英文版） . 2011,第10期
2. 5-Hydroxymethylcytosine in E-box motifs ACATGTG and ACACGTG increases DNA-binding of the B-HLH transcription factor TCF4 [J] . Khund-Sayeed Syed, He Ximiao, Holzberg TimothyWang JunRajagopal DivyaUpadhyay ShriyashDurell Stewart R.Mukherjee SanjitWeirauch Matthew T.Rose RobertVinson Charles Integrative Biology: quantitative biosciences from nano to macro . 2016,第9期

机译：5-Hydroxymethylcytosine in E-box motifs ACATGTG and ACACGTG increases DNA-binding of the B-HLH transcription factor TCF4
3. A Novel DNA Binding Protein That Recognizes the Methylated c-Myc Binding Motif1 [J] . IsaoSuetake, ShojiTajima, AkiraAsano The Journal of Biochemistry . 1995,第1期

机译：A Novel DNA Binding Protein That Recognizes the Methylated c-Myc Binding Motif1
4. Production of Anti-c-Myc Monoclonal Antibody Inhibiting DNA Binding of c-Myc and Max Dimer by Epitope Peptide-CpG-DNA-Liposome Complex Without Carriers [J] . Park Byoung Kwon, Gautam Avishekh, Maharjan SonyLee Su InLee YoungheeKwon Hyung-Joo International journal of peptide research and therapeutics . 2019,第1期

机译：Production of Anti-c-Myc Monoclonal Antibody Inhibiting DNA Binding of c-Myc and Max Dimer by Epitope Peptide-CpG-DNA-Liposome Complex Without Carriers
5. Sequence-specific DNA binding by MYC/MAX to low-affinity non-E-box motifs [O] . Michael Allevato, Eugene Bolotin, Mark Grossman, 2011

机译：MYC / MAX与低亲和力非E-box基序结合的序列特异性DNA
6. pp32 (ANP32A) expression inhibits pancreatic cancer cell growth and induces gemcitabine resistance by disrupting HuR binding to mRNAs. [O] . Williams, Timothy K, Costantino, Christina L, Bildzukewicz, Nikolai A, 2010

机译：pp32 (aNp32a) expression inhibits pancreatic cancer cell growth and induces gemcitabine resistance by disrupting HuR binding to mRNas.

Inhibiting MYC binding to the E-box DNA motif by ME47 decreases tumour xenograft growth

摘要

著录项

相似文献

相关主题

期刊订阅