Stabilization of the c-myc gene promoter quadruplex by specific ligands’ inhibitors of telomerase
| Autor: | Jean-François Riou, Eliane Mandine, Rajaa Paterski, Dennis Gomez, Patrick Mailliet, Thibault Lemarteleur |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Telomerase
Guanine Biophysics Biology Ligands G-quadruplex Polymerase Chain Reaction Biochemistry Telomestatin chemistry.chemical_compound Transcription (biology) Enzyme Stability heterocyclic compounds Enzyme Inhibitors Binding site Promoter Regions Genetic Molecular Biology Binding Sites Triazines Oligonucleotide Quinolinium Compounds Promoter Cell Biology Molecular biology Protein Structure Tertiary DNA-Binding Proteins Enzyme Activation chemistry Protein Binding Transcription Factors |
| Zdroj: | Biochemical and Biophysical Research Communications. 323:802-808 |
| ISSN: | 0006-291X |
| Popis: | A parallel G-quadruplex structure was recently identified in the NHE III(1) element of the c-myc gene promoter that functioned as a transcriptional repressor. Different series of telomeric G-quadruplex interacting ligands reported to block telomerase activity were evaluated in a new PCR stop assay on the c-myc quadruplex (Pu22myc). Results indicated that the cationic porphyrin TMPyP4 previously described to stabilize c-myc quadruplex and to cause transcription inhibition efficiently inhibited the assay but with a narrow selectivity when parallel experiments were performed with an oligonucleotide (Pu22mu) containing mutations in the guanine repeat which is unable to form a quadruplex. Other ligands presented potent inhibitory properties with IC(50) in the submicromolar range. 307A, a new 2,6-pyridin-dicarboxamide derivative was found to present the highest selectivity as compared to Pu22mu oligonucleotide (>90-fold). Comparison with telomeric G-quadruplex using TRAP-G4 and PCR stop assays also indicated that ligands 307A, telomestatin, and TMPyP4 are equipotent against both c-myc and telomeric sequences while other ligands displayed some partial selectivity (2- to 6-fold) towards one of these sequences. This work provides evidence that G-quadruplex ligands reported as telomerase inhibitors efficiently stabilized c-myc promoter intramolecular quadruplex and may also potentially be used to inhibit c-myc gene transcription in tumor cells. |
| Databáze: | OpenAIRE |
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