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The anti‐human cytomegalovirus drug tricin inhibits cyclin‐dependent kinase 9

4′,5,7‐trihydroxy‐3′,5′‐dimethoxyflavone (tricin), derived from Sasa albo‐marginata, has been reported to suppress significantly human cytomegalovirus (HCMV) replication in human embryonic lung (HEL) fibroblast cells. However, the target protein of tricin remains unclear. This study focused on the a...

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Autores principales: Sadanari, Hidetaka, Fujimoto, Kazuhiro J., Sugihara, Yuto, Ishida, Tomoki, Takemoto, Masaya, Daikoku, Tohru, Murayama, Tsugiya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881553/
https://www.ncbi.nlm.nih.gov/pubmed/29632816
http://dx.doi.org/10.1002/2211-5463.12398
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author Sadanari, Hidetaka
Fujimoto, Kazuhiro J.
Sugihara, Yuto
Ishida, Tomoki
Takemoto, Masaya
Daikoku, Tohru
Murayama, Tsugiya
author_facet Sadanari, Hidetaka
Fujimoto, Kazuhiro J.
Sugihara, Yuto
Ishida, Tomoki
Takemoto, Masaya
Daikoku, Tohru
Murayama, Tsugiya
author_sort Sadanari, Hidetaka
collection PubMed
description 4′,5,7‐trihydroxy‐3′,5′‐dimethoxyflavone (tricin), derived from Sasa albo‐marginata, has been reported to suppress significantly human cytomegalovirus (HCMV) replication in human embryonic lung (HEL) fibroblast cells. However, the target protein of tricin remains unclear. This study focused on the anti‐HCMV activity of tricin in terms of its binding affinity to cyclin‐dependent kinase 9 (CDK9). A molecular docking study predicted that tricin binds well to the ATP‐binding site of CDK9. Experimental measurements then revealed that tricin inhibits the kinase activity of CDK9 and affects the phosphorylation of the carboxy‐terminal domain of RNA polymerase II. Based on these results, we conclude that CDK9 is one of the target proteins of tricin. We also found that tricin possesses anti‐HCMV activity with no cytotoxicity against HEL cells.
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spelling pubmed-58815532018-04-09 The anti‐human cytomegalovirus drug tricin inhibits cyclin‐dependent kinase 9 Sadanari, Hidetaka Fujimoto, Kazuhiro J. Sugihara, Yuto Ishida, Tomoki Takemoto, Masaya Daikoku, Tohru Murayama, Tsugiya FEBS Open Bio Research Articles 4′,5,7‐trihydroxy‐3′,5′‐dimethoxyflavone (tricin), derived from Sasa albo‐marginata, has been reported to suppress significantly human cytomegalovirus (HCMV) replication in human embryonic lung (HEL) fibroblast cells. However, the target protein of tricin remains unclear. This study focused on the anti‐HCMV activity of tricin in terms of its binding affinity to cyclin‐dependent kinase 9 (CDK9). A molecular docking study predicted that tricin binds well to the ATP‐binding site of CDK9. Experimental measurements then revealed that tricin inhibits the kinase activity of CDK9 and affects the phosphorylation of the carboxy‐terminal domain of RNA polymerase II. Based on these results, we conclude that CDK9 is one of the target proteins of tricin. We also found that tricin possesses anti‐HCMV activity with no cytotoxicity against HEL cells. John Wiley and Sons Inc. 2018-02-20 /pmc/articles/PMC5881553/ /pubmed/29632816 http://dx.doi.org/10.1002/2211-5463.12398 Text en © 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Sadanari, Hidetaka
Fujimoto, Kazuhiro J.
Sugihara, Yuto
Ishida, Tomoki
Takemoto, Masaya
Daikoku, Tohru
Murayama, Tsugiya
The anti‐human cytomegalovirus drug tricin inhibits cyclin‐dependent kinase 9
title The anti‐human cytomegalovirus drug tricin inhibits cyclin‐dependent kinase 9
title_full The anti‐human cytomegalovirus drug tricin inhibits cyclin‐dependent kinase 9
title_fullStr The anti‐human cytomegalovirus drug tricin inhibits cyclin‐dependent kinase 9
title_full_unstemmed The anti‐human cytomegalovirus drug tricin inhibits cyclin‐dependent kinase 9
title_short The anti‐human cytomegalovirus drug tricin inhibits cyclin‐dependent kinase 9
title_sort anti‐human cytomegalovirus drug tricin inhibits cyclin‐dependent kinase 9
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881553/
https://www.ncbi.nlm.nih.gov/pubmed/29632816
http://dx.doi.org/10.1002/2211-5463.12398
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