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A novel yeast cell-based screen identifies flavone as a tankyrase inhibitor.

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.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Yashiroda Y,Okamoto R,Hatsugai K,Takemoto Y,Goshima N,Saito T,Hamamoto M,Sugimoto Y,Osada H,Seimiya H,Yoshida M

doi

10.1016/j.bbrc.2010.03.021

subject

Has Abstract

pub_date

2010-04-09 00:00:00

pages

569-73

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(10)00458-4

journal_volume

394

pub_type

杂志文章

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