Targeting Post-Translational Regulation of p53 in Colorectal Cancer by Exploiting Vulnerabilities in the p53-MDM2 Axis
The role played by the key tumor suppressor gene p53 and the implications of p53 mutations for the development and progression of neoplasia continue to expand. This review focuses on colorectal cancer and the regulators of p53 expression and activity identified over the past decade. These newly reco...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-01-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/14/1/219 |
| _version_ | 1797499342343372800 |
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| author | Chunwei W. Lai Cindy Xie Jean-Pierre Raufman Guofeng Xie |
| author_facet | Chunwei W. Lai Cindy Xie Jean-Pierre Raufman Guofeng Xie |
| author_sort | Chunwei W. Lai |
| collection | DOAJ |
| description | The role played by the key tumor suppressor gene p53 and the implications of p53 mutations for the development and progression of neoplasia continue to expand. This review focuses on colorectal cancer and the regulators of p53 expression and activity identified over the past decade. These newly recognized regulatory mechanisms include (1) direct regulation of mouse double minute 2 homolog (MDM2), an E3 ubiquitin-protein ligase; (2) modulation of the MDM2-p53 interaction; (3) MDM2-independent p53 degradation; and (4) inhibition of p53 nuclear translocation. We positioned these regulatory mechanisms in the context of p53 missense mutations, which not only evade canonical p53 degradation machinery but also exhibit gain-of-function phenotypes that enhance tumor survival and metastasis. Lastly, we discuss current and potential therapeutic strategies directed against p53 mutant-bearing tumors. |
| first_indexed | 2024-03-10T03:46:03Z |
| format | Article |
| id | doaj.art-11be849760454c12b241ad009eac572f |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T03:46:03Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-11be849760454c12b241ad009eac572f2023-11-23T11:17:59ZengMDPI AGCancers2072-66942022-01-0114121910.3390/cancers14010219Targeting Post-Translational Regulation of p53 in Colorectal Cancer by Exploiting Vulnerabilities in the p53-MDM2 AxisChunwei W. Lai0Cindy Xie1Jean-Pierre Raufman2Guofeng Xie3Department of Medicine, Division of Gastroenterology & Hepatology, University of Maryland School of Medicine, Baltimore, MD 21201, USADepartment of Medicine, Division of Gastroenterology & Hepatology, University of Maryland School of Medicine, Baltimore, MD 21201, USADepartment of Medicine, Division of Gastroenterology & Hepatology, University of Maryland School of Medicine, Baltimore, MD 21201, USADepartment of Medicine, Division of Gastroenterology & Hepatology, University of Maryland School of Medicine, Baltimore, MD 21201, USAThe role played by the key tumor suppressor gene p53 and the implications of p53 mutations for the development and progression of neoplasia continue to expand. This review focuses on colorectal cancer and the regulators of p53 expression and activity identified over the past decade. These newly recognized regulatory mechanisms include (1) direct regulation of mouse double minute 2 homolog (MDM2), an E3 ubiquitin-protein ligase; (2) modulation of the MDM2-p53 interaction; (3) MDM2-independent p53 degradation; and (4) inhibition of p53 nuclear translocation. We positioned these regulatory mechanisms in the context of p53 missense mutations, which not only evade canonical p53 degradation machinery but also exhibit gain-of-function phenotypes that enhance tumor survival and metastasis. Lastly, we discuss current and potential therapeutic strategies directed against p53 mutant-bearing tumors.https://www.mdpi.com/2072-6694/14/1/219degradationcolorectal cancerp53MDM2negative feedback |
| spellingShingle | Chunwei W. Lai Cindy Xie Jean-Pierre Raufman Guofeng Xie Targeting Post-Translational Regulation of p53 in Colorectal Cancer by Exploiting Vulnerabilities in the p53-MDM2 Axis Cancers degradation colorectal cancer p53 MDM2 negative feedback |
| title | Targeting Post-Translational Regulation of p53 in Colorectal Cancer by Exploiting Vulnerabilities in the p53-MDM2 Axis |
| title_full | Targeting Post-Translational Regulation of p53 in Colorectal Cancer by Exploiting Vulnerabilities in the p53-MDM2 Axis |
| title_fullStr | Targeting Post-Translational Regulation of p53 in Colorectal Cancer by Exploiting Vulnerabilities in the p53-MDM2 Axis |
| title_full_unstemmed | Targeting Post-Translational Regulation of p53 in Colorectal Cancer by Exploiting Vulnerabilities in the p53-MDM2 Axis |
| title_short | Targeting Post-Translational Regulation of p53 in Colorectal Cancer by Exploiting Vulnerabilities in the p53-MDM2 Axis |
| title_sort | targeting post translational regulation of p53 in colorectal cancer by exploiting vulnerabilities in the p53 mdm2 axis |
| topic | degradation colorectal cancer p53 MDM2 negative feedback |
| url | https://www.mdpi.com/2072-6694/14/1/219 |
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