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XPC promotes MDM2-mediated degradation of the p53 tumor suppressor
Although ubiquitin receptor Rad23 has been implicated in bringing ubiquitylated p53 to the proteasome, how Rad23 recognizes p53 remains unclear. We demonstrate that XPC, a Rad23-binding protein, regulates p53 turnover. p53 protein in XPC-deficient cells remains ubiquitylated, but its association wit...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3890342/ https://www.ncbi.nlm.nih.gov/pubmed/24258024 http://dx.doi.org/10.1091/mbc.E13-05-0293 |
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author | Krzeszinski, Jing Yan Choe, Vitnary Shao, Jia Bao, Xin Cheng, Haili Luo, Shiwen Huo, Keke Rao, Hai |
author_facet | Krzeszinski, Jing Yan Choe, Vitnary Shao, Jia Bao, Xin Cheng, Haili Luo, Shiwen Huo, Keke Rao, Hai |
author_sort | Krzeszinski, Jing Yan |
collection | PubMed |
description | Although ubiquitin receptor Rad23 has been implicated in bringing ubiquitylated p53 to the proteasome, how Rad23 recognizes p53 remains unclear. We demonstrate that XPC, a Rad23-binding protein, regulates p53 turnover. p53 protein in XPC-deficient cells remains ubiquitylated, but its association with the proteasome is drastically reduced, indicating that XPC regulates a postubiquitylation event. Furthermore, we found that XPC participates in the MDM2-mediated p53 degradation pathway via direct interaction with MDM2. XPC W690S pathogenic mutant is specifically defective for MDM2 binding and p53 degradation. p53 is known to become stabilized following UV irradiation but can be rendered unstable by XPC overexpression, underscoring a critical role of XPC in p53 regulation. Elucidation of the proteolytic role of XPC in cancer cells will help to unravel the detailed mechanisms underlying the coordination of DNA repair and proteolysis. |
format | Online Article Text |
id | pubmed-3890342 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-38903422014-03-30 XPC promotes MDM2-mediated degradation of the p53 tumor suppressor Krzeszinski, Jing Yan Choe, Vitnary Shao, Jia Bao, Xin Cheng, Haili Luo, Shiwen Huo, Keke Rao, Hai Mol Biol Cell Articles Although ubiquitin receptor Rad23 has been implicated in bringing ubiquitylated p53 to the proteasome, how Rad23 recognizes p53 remains unclear. We demonstrate that XPC, a Rad23-binding protein, regulates p53 turnover. p53 protein in XPC-deficient cells remains ubiquitylated, but its association with the proteasome is drastically reduced, indicating that XPC regulates a postubiquitylation event. Furthermore, we found that XPC participates in the MDM2-mediated p53 degradation pathway via direct interaction with MDM2. XPC W690S pathogenic mutant is specifically defective for MDM2 binding and p53 degradation. p53 is known to become stabilized following UV irradiation but can be rendered unstable by XPC overexpression, underscoring a critical role of XPC in p53 regulation. Elucidation of the proteolytic role of XPC in cancer cells will help to unravel the detailed mechanisms underlying the coordination of DNA repair and proteolysis. The American Society for Cell Biology 2014-01-15 /pmc/articles/PMC3890342/ /pubmed/24258024 http://dx.doi.org/10.1091/mbc.E13-05-0293 Text en © 2014 Krzeszinski et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Krzeszinski, Jing Yan Choe, Vitnary Shao, Jia Bao, Xin Cheng, Haili Luo, Shiwen Huo, Keke Rao, Hai XPC promotes MDM2-mediated degradation of the p53 tumor suppressor |
title | XPC promotes MDM2-mediated degradation of the p53 tumor suppressor |
title_full | XPC promotes MDM2-mediated degradation of the p53 tumor suppressor |
title_fullStr | XPC promotes MDM2-mediated degradation of the p53 tumor suppressor |
title_full_unstemmed | XPC promotes MDM2-mediated degradation of the p53 tumor suppressor |
title_short | XPC promotes MDM2-mediated degradation of the p53 tumor suppressor |
title_sort | xpc promotes mdm2-mediated degradation of the p53 tumor suppressor |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3890342/ https://www.ncbi.nlm.nih.gov/pubmed/24258024 http://dx.doi.org/10.1091/mbc.E13-05-0293 |
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