RRC ID 11942
Author Yashiroda Y, Okamoto R, Hatsugai K, Takemoto Y, Goshima N, Saito T, Hamamoto M, Sugimoto Y, Osada H, Seimiya H, Yoshida M.
Title A novel yeast cell-based screen identifies flavone as a tankyrase inhibitor.
Journal Biochem Biophys Res Commun
Abstract The telomere-associated protein tankyrase 1 is a poly(ADP-ribose) polymerase and is considered to be a promising target for cancer therapy, especially for BRCA-associated cancers. However, an efficient assay system for inhibitor screening has not been established, mainly due to the difficulty of efficient preparation of the enzyme and its substrate. Here, we report a cell-based assay system for detecting inhibitory activity against tankyrase 1. We found that overexpression of the human tankyrase 1 gene causes a growth defect in the fission yeast Schizosaccharomyces pombe. Chemicals that restore the growth defect phenotype can be identified as potential tankyrase 1 inhibitors. We performed a high-throughput screen using this system, and identified flavone as a compound that restores the growth of yeast cells overexpressing tankyrase 1. Indeed, flavone inhibited poly(ADP-ribosyl)ation of proteins caused by overexpression of tankyrase 1 in yeast cells. This system allows rapid identification of inhibitory activity against tankyrase 1 and is amenable to high-throughput screening using robotics.
Volume 394(3)
Pages 569-73
Published 2010-4-9
DOI 10.1016/j.bbrc.2010.03.021
PII S0006-291X(10)00458-4
PMID 20214890
MeSH Cell Line Drug Discovery / methods* Drug Evaluation, Preclinical Enzyme Inhibitors / chemistry Enzyme Inhibitors / isolation & purification* Enzyme Inhibitors / pharmacology Flavones Flavonoids / chemistry Flavonoids / isolation & purification* Flavonoids / pharmacology High-Throughput Screening Assays* Humans Schizosaccharomyces / drug effects Schizosaccharomyces / genetics Tankyrases / antagonists & inhibitors* Tankyrases / genetics
IF 2.705
Times Cited 28
DNA material pDUAL-FFH1c (RDB06142)