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TRIM3 inhibits P53 signaling in breast cancer cells
BACKGROUND: Beast cancer is the most common women cancer worldwide, while two third of them are ER alpha positive breast cancer. Among the ER alpha positive breast cancer, about 80% are P53 wild type, indicating the potential tumor suppression role in ER alpha positive breast cancer. Since P53 is an...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685606/ https://www.ncbi.nlm.nih.gov/pubmed/33292295 http://dx.doi.org/10.1186/s12935-020-01630-z |
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author | Wang, Xinxing Zhang, Yujie Pei, Xinhong Guo, Guangcheng Xue, Bingjian Duan, Xin Dou, Dongwei |
author_facet | Wang, Xinxing Zhang, Yujie Pei, Xinhong Guo, Guangcheng Xue, Bingjian Duan, Xin Dou, Dongwei |
author_sort | Wang, Xinxing |
collection | PubMed |
description | BACKGROUND: Beast cancer is the most common women cancer worldwide, while two third of them are ER alpha positive breast cancer. Among the ER alpha positive breast cancer, about 80% are P53 wild type, indicating the potential tumor suppression role in ER alpha positive breast cancer. Since P53 is an important safeguard to inhibit cell malignant transformation, reactivating P53 signaling could a plausible approach to treat breast cancer. METHODS: TRIM3 protein levels were measured by western blot, while the P53 classical target genes were measured by real-time PCR. WST1 assay were used to measure cell proliferation, while cleaved caspase-3 was used to detect cell apoptosis. Protein stability and ubiquitin assay were used to detect the P53 protein ubiquitin and stability. The immuno-precipitation assays were used to detect the protein interactions. Immuno-staining was used to detect the protein localization of P53 and TRIM3, while the ubiquitin-based immuno-precipitation assays were used to detect the specific ubiquitination manner of P53. RESULTS: In our study, we identified TRIM3 as an endogenous inhibitor for P53 signaling. TRIM3 depletion inhibited breast cancer cell proliferation and promoted apoptosis. In addition, TRIM3 depletion increased P53 protein level in breast cancer cell. Further investigation showed that TRIM3 could associate with P53 and promote P53 K48-linked ubiquitination and degradation. CONCLUSION: Our study identified a novel post-translational modification mechanism between TRIM3 and P53. TRIM3 depletion or blockage could be a promising strategy to rescue P53 signaling and inhibit breast cancer progression. |
format | Online Article Text |
id | pubmed-7685606 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-76856062020-11-25 TRIM3 inhibits P53 signaling in breast cancer cells Wang, Xinxing Zhang, Yujie Pei, Xinhong Guo, Guangcheng Xue, Bingjian Duan, Xin Dou, Dongwei Cancer Cell Int Primary Research BACKGROUND: Beast cancer is the most common women cancer worldwide, while two third of them are ER alpha positive breast cancer. Among the ER alpha positive breast cancer, about 80% are P53 wild type, indicating the potential tumor suppression role in ER alpha positive breast cancer. Since P53 is an important safeguard to inhibit cell malignant transformation, reactivating P53 signaling could a plausible approach to treat breast cancer. METHODS: TRIM3 protein levels were measured by western blot, while the P53 classical target genes were measured by real-time PCR. WST1 assay were used to measure cell proliferation, while cleaved caspase-3 was used to detect cell apoptosis. Protein stability and ubiquitin assay were used to detect the P53 protein ubiquitin and stability. The immuno-precipitation assays were used to detect the protein interactions. Immuno-staining was used to detect the protein localization of P53 and TRIM3, while the ubiquitin-based immuno-precipitation assays were used to detect the specific ubiquitination manner of P53. RESULTS: In our study, we identified TRIM3 as an endogenous inhibitor for P53 signaling. TRIM3 depletion inhibited breast cancer cell proliferation and promoted apoptosis. In addition, TRIM3 depletion increased P53 protein level in breast cancer cell. Further investigation showed that TRIM3 could associate with P53 and promote P53 K48-linked ubiquitination and degradation. CONCLUSION: Our study identified a novel post-translational modification mechanism between TRIM3 and P53. TRIM3 depletion or blockage could be a promising strategy to rescue P53 signaling and inhibit breast cancer progression. BioMed Central 2020-11-23 /pmc/articles/PMC7685606/ /pubmed/33292295 http://dx.doi.org/10.1186/s12935-020-01630-z Text en © The Author(s) 2020 Open AccessThis 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/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Primary Research Wang, Xinxing Zhang, Yujie Pei, Xinhong Guo, Guangcheng Xue, Bingjian Duan, Xin Dou, Dongwei TRIM3 inhibits P53 signaling in breast cancer cells |
title | TRIM3 inhibits P53 signaling in breast cancer cells |
title_full | TRIM3 inhibits P53 signaling in breast cancer cells |
title_fullStr | TRIM3 inhibits P53 signaling in breast cancer cells |
title_full_unstemmed | TRIM3 inhibits P53 signaling in breast cancer cells |
title_short | TRIM3 inhibits P53 signaling in breast cancer cells |
title_sort | trim3 inhibits p53 signaling in breast cancer cells |
topic | Primary Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685606/ https://www.ncbi.nlm.nih.gov/pubmed/33292295 http://dx.doi.org/10.1186/s12935-020-01630-z |
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