Drug Targeting of the c-MYC Promoter to Repress Gene Expression via a G-Quadruplex Silencer Element

Laurence H. Hurley, Daniel D. Von Hoff, Adam Siddiqui-Jain, Danzhou Yang

Research output: Contribution to journalArticlepeer-review

98 Scopus citations

Abstract

In this review, we describe the evidence for a parallel-stranded G-quadruplex in the purine-rich strand of the nuclease hypersensitivity element III1 (NHE III1) of the promoter of c-MYC upstream of the P1 and P2 promoters. This biologically relevant G-quadruplex is a mixture of four loop isomers. The folding pattern of a nuclear magnetic resonance (NMR)-derived structure for the predominant loop isomer of this G-quadruplex has been obtained. This G-quadruplex has been demonstrated to be a silencer element, and the cationic porphyrin TMPyP4 has been shown to stabilize this G-quadruplex. Furthermore, TMPyP4 has been shown to repress c-MYC expression, and this effect is mediated through the silencer element. Last, the in vivo activity of TMPyP4 in xenograph models is presented.

Original languageEnglish (US)
Pages (from-to)498-512
Number of pages15
JournalSeminars in Oncology
Volume33
Issue number4
DOIs
StatePublished - Aug 1 2006

ASJC Scopus subject areas

  • Hematology
  • Oncology

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