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Establishment of high-throughput screening HTRF assay for identification small molecule inhibitors of Skp2-Cks1

S-phase kinase associated protein 2 (Skp2), a member of the F-box family that constitute the largest known class of ubiquitin E3 specificity components, is responsible for recognizing and recruiting cyclin-dependent kinase inhibitor p27 for its ubiquitination in the presence of the small accessory p...

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Autores principales: Hu, Kaizhao, Li, Xiao-Jing, Asmamaw, Moges Dessale, Shi, Xiao-Jing, Liu, Hong-Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8548536/
https://www.ncbi.nlm.nih.gov/pubmed/34702937
http://dx.doi.org/10.1038/s41598-021-00646-3
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author Hu, Kaizhao
Li, Xiao-Jing
Asmamaw, Moges Dessale
Shi, Xiao-Jing
Liu, Hong-Min
author_facet Hu, Kaizhao
Li, Xiao-Jing
Asmamaw, Moges Dessale
Shi, Xiao-Jing
Liu, Hong-Min
author_sort Hu, Kaizhao
collection PubMed
description S-phase kinase associated protein 2 (Skp2), a member of the F-box family that constitute the largest known class of ubiquitin E3 specificity components, is responsible for recognizing and recruiting cyclin-dependent kinase inhibitor p27 for its ubiquitination in the presence of the small accessory protein cyclin-dependent kinase regulatory subunit 1(Cks1). Skp2 is overexpressed in esophageal carcinoma tissues and closely related with tumor poor prognosis, and perturbation of the Skp2-Cks1 interaction by inhibitors or RNAi could inhibit the proliferation and metastasis of tumor cells. Therefore, inhibition of Skp2 function by small-molecule compounds targeting Skp2-Cks1 interaction is emerging as a promising and novel anti-cancer strategy. In this study, we establish an improved high-throughput screening platform to screen Skp2 inhibitors targeting Skp2-Cks1interaction, which may provide a new therapeutic approach for the clinic.
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spelling pubmed-85485362021-10-28 Establishment of high-throughput screening HTRF assay for identification small molecule inhibitors of Skp2-Cks1 Hu, Kaizhao Li, Xiao-Jing Asmamaw, Moges Dessale Shi, Xiao-Jing Liu, Hong-Min Sci Rep Article S-phase kinase associated protein 2 (Skp2), a member of the F-box family that constitute the largest known class of ubiquitin E3 specificity components, is responsible for recognizing and recruiting cyclin-dependent kinase inhibitor p27 for its ubiquitination in the presence of the small accessory protein cyclin-dependent kinase regulatory subunit 1(Cks1). Skp2 is overexpressed in esophageal carcinoma tissues and closely related with tumor poor prognosis, and perturbation of the Skp2-Cks1 interaction by inhibitors or RNAi could inhibit the proliferation and metastasis of tumor cells. Therefore, inhibition of Skp2 function by small-molecule compounds targeting Skp2-Cks1 interaction is emerging as a promising and novel anti-cancer strategy. In this study, we establish an improved high-throughput screening platform to screen Skp2 inhibitors targeting Skp2-Cks1interaction, which may provide a new therapeutic approach for the clinic. Nature Publishing Group UK 2021-10-26 /pmc/articles/PMC8548536/ /pubmed/34702937 http://dx.doi.org/10.1038/s41598-021-00646-3 Text en © The Author(s) 2021, corrected publication 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Hu, Kaizhao
Li, Xiao-Jing
Asmamaw, Moges Dessale
Shi, Xiao-Jing
Liu, Hong-Min
Establishment of high-throughput screening HTRF assay for identification small molecule inhibitors of Skp2-Cks1
title Establishment of high-throughput screening HTRF assay for identification small molecule inhibitors of Skp2-Cks1
title_full Establishment of high-throughput screening HTRF assay for identification small molecule inhibitors of Skp2-Cks1
title_fullStr Establishment of high-throughput screening HTRF assay for identification small molecule inhibitors of Skp2-Cks1
title_full_unstemmed Establishment of high-throughput screening HTRF assay for identification small molecule inhibitors of Skp2-Cks1
title_short Establishment of high-throughput screening HTRF assay for identification small molecule inhibitors of Skp2-Cks1
title_sort establishment of high-throughput screening htrf assay for identification small molecule inhibitors of skp2-cks1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8548536/
https://www.ncbi.nlm.nih.gov/pubmed/34702937
http://dx.doi.org/10.1038/s41598-021-00646-3
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