| 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 |
2.985
|
| Times Cited |
28
|
|
WOS Category
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| DNA material |
pDUAL-FFH1c (RDB06142) |
