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Regulation of the p53 Family Proteins by the Ubiquitin Proteasomal Pathway
The tumor suppressor p53 and its homologues, p63 and p73, play a pivotal role in the regulation of the DNA damage response, cellular homeostasis, development, aging, and metabolism. A number of mouse studies have shown that a genetic defect in the p53 family could lead to spontaneous tumor developme...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981958/ https://www.ncbi.nlm.nih.gov/pubmed/31905981 http://dx.doi.org/10.3390/ijms21010261 |
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author | Bang, Scott Kaur, Sandeep Kurokawa, Manabu |
author_facet | Bang, Scott Kaur, Sandeep Kurokawa, Manabu |
author_sort | Bang, Scott |
collection | PubMed |
description | The tumor suppressor p53 and its homologues, p63 and p73, play a pivotal role in the regulation of the DNA damage response, cellular homeostasis, development, aging, and metabolism. A number of mouse studies have shown that a genetic defect in the p53 family could lead to spontaneous tumor development, embryonic lethality, or severe tissue abnormality, indicating that the activity of the p53 family must be tightly regulated to maintain normal cellular functions. While the p53 family members are regulated at the level of gene expression as well as post-translational modification, they are also controlled at the level of protein stability through the ubiquitin proteasomal pathway. Over the last 20 years, many ubiquitin E3 ligases have been discovered that directly promote protein degradation of p53, p63, and p73 in vitro and in vivo. Here, we provide an overview of such E3 ligases and discuss their roles and functions. |
format | Online Article Text |
id | pubmed-6981958 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-69819582020-02-07 Regulation of the p53 Family Proteins by the Ubiquitin Proteasomal Pathway Bang, Scott Kaur, Sandeep Kurokawa, Manabu Int J Mol Sci Review The tumor suppressor p53 and its homologues, p63 and p73, play a pivotal role in the regulation of the DNA damage response, cellular homeostasis, development, aging, and metabolism. A number of mouse studies have shown that a genetic defect in the p53 family could lead to spontaneous tumor development, embryonic lethality, or severe tissue abnormality, indicating that the activity of the p53 family must be tightly regulated to maintain normal cellular functions. While the p53 family members are regulated at the level of gene expression as well as post-translational modification, they are also controlled at the level of protein stability through the ubiquitin proteasomal pathway. Over the last 20 years, many ubiquitin E3 ligases have been discovered that directly promote protein degradation of p53, p63, and p73 in vitro and in vivo. Here, we provide an overview of such E3 ligases and discuss their roles and functions. MDPI 2019-12-30 /pmc/articles/PMC6981958/ /pubmed/31905981 http://dx.doi.org/10.3390/ijms21010261 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Bang, Scott Kaur, Sandeep Kurokawa, Manabu Regulation of the p53 Family Proteins by the Ubiquitin Proteasomal Pathway |
title | Regulation of the p53 Family Proteins by the Ubiquitin Proteasomal Pathway |
title_full | Regulation of the p53 Family Proteins by the Ubiquitin Proteasomal Pathway |
title_fullStr | Regulation of the p53 Family Proteins by the Ubiquitin Proteasomal Pathway |
title_full_unstemmed | Regulation of the p53 Family Proteins by the Ubiquitin Proteasomal Pathway |
title_short | Regulation of the p53 Family Proteins by the Ubiquitin Proteasomal Pathway |
title_sort | regulation of the p53 family proteins by the ubiquitin proteasomal pathway |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981958/ https://www.ncbi.nlm.nih.gov/pubmed/31905981 http://dx.doi.org/10.3390/ijms21010261 |
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