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Small molecule activators of the p53 response
Drugging the p53 pathway has been a goal for both academics and pharmaceutical companies since the designation of p53 as the ‘guardian of the genome’. Through growing understanding of p53 biology, we can see multiple routes for activation of both wild-type p53 function and restoration of mutant p53....
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478124/ https://www.ncbi.nlm.nih.gov/pubmed/30689917 http://dx.doi.org/10.1093/jmcb/mjz006 |
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author | Ladds, Marcus J G W Laín, Sonia |
author_facet | Ladds, Marcus J G W Laín, Sonia |
author_sort | Ladds, Marcus J G W |
collection | PubMed |
description | Drugging the p53 pathway has been a goal for both academics and pharmaceutical companies since the designation of p53 as the ‘guardian of the genome’. Through growing understanding of p53 biology, we can see multiple routes for activation of both wild-type p53 function and restoration of mutant p53. In this review, we focus on small molecules that activate wild-type p53 and that do so in a non-genotoxic manner. In particular, we will describe potential approaches to targeting proteins that alter p53 stability and function through posttranslational modification, affect p53’s subcellular localization, or target RNA synthesis or the synthesis of ribonucleotides. The plethora of pathways for exploitation of p53, as well as the wide-ranging response to p53 activation, makes it an attractive target for anti-cancer therapy. |
format | Online Article Text |
id | pubmed-6478124 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-64781242019-04-25 Small molecule activators of the p53 response Ladds, Marcus J G W Laín, Sonia J Mol Cell Biol Invited Review Drugging the p53 pathway has been a goal for both academics and pharmaceutical companies since the designation of p53 as the ‘guardian of the genome’. Through growing understanding of p53 biology, we can see multiple routes for activation of both wild-type p53 function and restoration of mutant p53. In this review, we focus on small molecules that activate wild-type p53 and that do so in a non-genotoxic manner. In particular, we will describe potential approaches to targeting proteins that alter p53 stability and function through posttranslational modification, affect p53’s subcellular localization, or target RNA synthesis or the synthesis of ribonucleotides. The plethora of pathways for exploitation of p53, as well as the wide-ranging response to p53 activation, makes it an attractive target for anti-cancer therapy. Oxford University Press 2019-01-25 /pmc/articles/PMC6478124/ /pubmed/30689917 http://dx.doi.org/10.1093/jmcb/mjz006 Text en © The Author(s) (2019). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Invited Review Ladds, Marcus J G W Laín, Sonia Small molecule activators of the p53 response |
title | Small molecule activators of the p53 response |
title_full | Small molecule activators of the p53 response |
title_fullStr | Small molecule activators of the p53 response |
title_full_unstemmed | Small molecule activators of the p53 response |
title_short | Small molecule activators of the p53 response |
title_sort | small molecule activators of the p53 response |
topic | Invited Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478124/ https://www.ncbi.nlm.nih.gov/pubmed/30689917 http://dx.doi.org/10.1093/jmcb/mjz006 |
work_keys_str_mv | AT laddsmarcusjgw smallmoleculeactivatorsofthep53response AT lainsonia smallmoleculeactivatorsofthep53response |