Development of a novel immunoassay to detect interactions with the transactivation domain of p53: application to screening of new drugs

Abstract Tumor protein p53 acts as a trans-activator that negatively regulates cell division by controlling a set of genes required for cell cycle regulation, making it a tumor suppressor in different types of tumors. Because the transcriptional activity of p53 plays an important role in the occurre...

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Autores principales:	Yufeng Xiong, Yingsong Wu, Shuhong Luo, Yang Gao, Yujing Xiong, Daxiang Chen, Hao Deng, Wenbo Hao, Tiancai Liu, Ming Li
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/838d43d4090a434cbc14ccf27143dbda
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spelling	oai:doaj.org-article:838d43d4090a434cbc14ccf27143dbda2021-12-02T12:32:25ZDevelopment of a novel immunoassay to detect interactions with the transactivation domain of p53: application to screening of new drugs10.1038/s41598-017-09574-72045-2322https://doaj.org/article/838d43d4090a434cbc14ccf27143dbda2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09574-7https://doaj.org/toc/2045-2322Abstract Tumor protein p53 acts as a trans-activator that negatively regulates cell division by controlling a set of genes required for cell cycle regulation, making it a tumor suppressor in different types of tumors. Because the transcriptional activity of p53 plays an important role in the occurrence and development of tumors, reactivation of p53 transcriptional activity has been sought as a novel cancer therapeutic strategy. There is great interest in developing high-throughput assays to identify inhibitors of molecules that bind the transcription-activation domain of p53, especially for wt p53-containing tumors. In the present study, taking MDM2 as an example, a novel amplified luminescent proximity homogeneous assay (AlphaLISA) was modified from a binding competition assay to detect the interactions between the transcription-activation domain of p53 and its ligands. This assay can be adapted as a high-throughput assay for screening new inhibitors. A panel of well-known p53-MDM2 binding inhibitors was used to validate this method, and demonstrated its utility, sensitivity and robustness. In summary, we have developed a novel protein-protein interaction detection immunoassay that can be used in a high-throughput format to screen new drug candidates for reactivation of p53. This assay has been successfully validated through a series of p53-MDM2 binding inhibitors.Yufeng XiongYingsong WuShuhong LuoYang GaoYujing XiongDaxiang ChenHao DengWenbo HaoTiancai LiuMing LiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yufeng Xiong Yingsong Wu Shuhong Luo Yang Gao Yujing Xiong Daxiang Chen Hao Deng Wenbo Hao Tiancai Liu Ming Li Development of a novel immunoassay to detect interactions with the transactivation domain of p53: application to screening of new drugs
description	Abstract Tumor protein p53 acts as a trans-activator that negatively regulates cell division by controlling a set of genes required for cell cycle regulation, making it a tumor suppressor in different types of tumors. Because the transcriptional activity of p53 plays an important role in the occurrence and development of tumors, reactivation of p53 transcriptional activity has been sought as a novel cancer therapeutic strategy. There is great interest in developing high-throughput assays to identify inhibitors of molecules that bind the transcription-activation domain of p53, especially for wt p53-containing tumors. In the present study, taking MDM2 as an example, a novel amplified luminescent proximity homogeneous assay (AlphaLISA) was modified from a binding competition assay to detect the interactions between the transcription-activation domain of p53 and its ligands. This assay can be adapted as a high-throughput assay for screening new inhibitors. A panel of well-known p53-MDM2 binding inhibitors was used to validate this method, and demonstrated its utility, sensitivity and robustness. In summary, we have developed a novel protein-protein interaction detection immunoassay that can be used in a high-throughput format to screen new drug candidates for reactivation of p53. This assay has been successfully validated through a series of p53-MDM2 binding inhibitors.
format	article
author	Yufeng Xiong Yingsong Wu Shuhong Luo Yang Gao Yujing Xiong Daxiang Chen Hao Deng Wenbo Hao Tiancai Liu Ming Li
author_facet	Yufeng Xiong Yingsong Wu Shuhong Luo Yang Gao Yujing Xiong Daxiang Chen Hao Deng Wenbo Hao Tiancai Liu Ming Li
author_sort	Yufeng Xiong
title	Development of a novel immunoassay to detect interactions with the transactivation domain of p53: application to screening of new drugs
title_short	Development of a novel immunoassay to detect interactions with the transactivation domain of p53: application to screening of new drugs
title_full	Development of a novel immunoassay to detect interactions with the transactivation domain of p53: application to screening of new drugs
title_fullStr	Development of a novel immunoassay to detect interactions with the transactivation domain of p53: application to screening of new drugs
title_full_unstemmed	Development of a novel immunoassay to detect interactions with the transactivation domain of p53: application to screening of new drugs
title_sort	development of a novel immunoassay to detect interactions with the transactivation domain of p53: application to screening of new drugs
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/838d43d4090a434cbc14ccf27143dbda
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Development of a novel immunoassay to detect interactions with the transactivation domain of p53: application to screening of new drugs

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