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  • 标题:Identification of small molecules that induce apoptosis in a Myc-dependent manner and inhibit Myc-driven transformation
  • 本地全文:下载
  • 作者:Hao Mo ; Marie Henriksson
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2006
  • 卷号:103
  • 期号:16
  • 页码:6344-6349
  • DOI:10.1073/pnas.0601418103
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:The Myc transcription factor plays a central role in the regulation of cell cycle progression, apoptosis, angiogenesis, and cellular transformation. Myc is a potent oncoprotein that is deregulated in a wide variety of human tumors and is therefore an attractive target for novel cancer therapies. Using a cellular screening approach, we have identified low-molecular-weight compounds, Myc pathway response agents (MYRAs), that induce apoptosis in a c-Myc-dependent manner and inhibit Myc-driven cellular transformation. MYRA-A inhibits Myc transactivation and interferes with the DNA-binding activity of Myc family proteins but has no effect on the E-box-binding protein USF. In contrast, MYRA-B induces Myc-dependent apoptosis without affecting Myc transactivation or Myc/Max DNA binding. Our data show that cellular screening assays can be a powerful strategy for the identification of candidate substances that modulate the Myc pathway. These compounds can be useful tools for studying Myc function and may also be of therapeutic potential as leads for drug development.
  • 关键词:cellular screen ; chemical library ; proliferation ; Myc pathway ; DNA-binding
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