TY - JOUR
T1 - A novel yeast cell-based screen identifies flavone as a tankyrase inhibitor
AU - Yashiroda, Yoko
AU - Okamoto, Reika
AU - Hatsugai, Kaori
AU - Takemoto, Yasushi
AU - Goshima, Naoki
AU - Saito, Tamio
AU - Hamamoto, Makiko
AU - Sugimoto, Yoshikazu
AU - Osada, Hiroyuki
AU - Seimiya, Hiroyuki
AU - Yoshida, Minoru
N1 - Funding Information:
We are grateful to the RIKEN Brain Science Institute’s Research Resources Center for DNA sequencing analysis. This work was supported in part by the Strategic Research Programs for R&D , RIKEN, a grant from the New Energy and Industrial Technology Department Organization (NEDO) of Japan , and the CREST Research Project .
PY - 2010/4/9
Y1 - 2010/4/9
N2 - 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.
AB - 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.
KW - High-throughput screening
KW - Inhibitor
KW - Schizosaccharomyces pombe
KW - Tankyrase 1
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U2 - 10.1016/j.bbrc.2010.03.021
DO - 10.1016/j.bbrc.2010.03.021
M3 - Article
C2 - 20214890
AN - SCOPUS:77950519035
SN - 0006-291X
VL - 394
SP - 569
EP - 573
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -
