TY - JOUR
T1 - Drug Targeting of the c-MYC Promoter to Repress Gene Expression via a G-Quadruplex Silencer Element
AU - Hurley, Laurence H.
AU - Von Hoff, Daniel D.
AU - Siddiqui-Jain, Adam
AU - Yang, Danzhou
PY - 2006/8
Y1 - 2006/8
N2 - 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.
AB - 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.
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U2 - 10.1053/j.seminoncol.2006.04.012
DO - 10.1053/j.seminoncol.2006.04.012
M3 - Article
C2 - 16890804
AN - SCOPUS:33746520122
SN - 0093-7754
VL - 33
SP - 498
EP - 512
JO - Seminars in Oncology
JF - Seminars in Oncology
IS - 4
ER -