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Expanding the prion concept to cancer biology: dominant-negative effect of aggregates of mutant p53 tumour suppressor
p53 is a key protein that participates in cell-cycle control, and its malfunction can lead to cancer. This tumour suppressor protein has three main domains; the N-terminal transactivation domain, the CTD (C-terminal domain) and the core domain (p53C) that constitutes the sequence-specific DBD (DNA-b...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3728989/ https://www.ncbi.nlm.nih.gov/pubmed/24003888 http://dx.doi.org/10.1042/BSR20130065 |
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author | Silva, Jerson L. Rangel, Luciana P. Costa, Danielly C. F. Cordeiro, Yraima De Moura Gallo, Claudia V. |
author_facet | Silva, Jerson L. Rangel, Luciana P. Costa, Danielly C. F. Cordeiro, Yraima De Moura Gallo, Claudia V. |
author_sort | Silva, Jerson L. |
collection | PubMed |
description | p53 is a key protein that participates in cell-cycle control, and its malfunction can lead to cancer. This tumour suppressor protein has three main domains; the N-terminal transactivation domain, the CTD (C-terminal domain) and the core domain (p53C) that constitutes the sequence-specific DBD (DNA-binding region). Most p53 mutations related to cancer development are found in the DBD. Aggregation of p53 into amyloid oligomers and fibrils has been shown. Moreover, amyloid aggregates of both the mutant and WT (wild-type) forms of p53 were detected in tumour tissues. We propose that if p53 aggregation occurred, it would be a crucial aspect of cancer development, as p53 would lose its WT functions in an aggregated state. Mutant p53 can also exert a dominant-negative regulatory effect on WT p53. Herein, we discuss the dominant-negative effect in light of p53 aggregation and the fact that amyloid-like mutant p53 can convert WT p53 into more aggregated species, leading into gain of function in addition to the loss of tumour suppressor function. In summary, the results obtained in the last decade indicate that cancer may have characteristics in common with amyloidogenic and prion diseases. |
format | Online Article Text |
id | pubmed-3728989 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-37289892013-08-09 Expanding the prion concept to cancer biology: dominant-negative effect of aggregates of mutant p53 tumour suppressor Silva, Jerson L. Rangel, Luciana P. Costa, Danielly C. F. Cordeiro, Yraima De Moura Gallo, Claudia V. Biosci Rep Review Article p53 is a key protein that participates in cell-cycle control, and its malfunction can lead to cancer. This tumour suppressor protein has three main domains; the N-terminal transactivation domain, the CTD (C-terminal domain) and the core domain (p53C) that constitutes the sequence-specific DBD (DNA-binding region). Most p53 mutations related to cancer development are found in the DBD. Aggregation of p53 into amyloid oligomers and fibrils has been shown. Moreover, amyloid aggregates of both the mutant and WT (wild-type) forms of p53 were detected in tumour tissues. We propose that if p53 aggregation occurred, it would be a crucial aspect of cancer development, as p53 would lose its WT functions in an aggregated state. Mutant p53 can also exert a dominant-negative regulatory effect on WT p53. Herein, we discuss the dominant-negative effect in light of p53 aggregation and the fact that amyloid-like mutant p53 can convert WT p53 into more aggregated species, leading into gain of function in addition to the loss of tumour suppressor function. In summary, the results obtained in the last decade indicate that cancer may have characteristics in common with amyloidogenic and prion diseases. Portland Press Ltd. 2013-07-25 /pmc/articles/PMC3728989/ /pubmed/24003888 http://dx.doi.org/10.1042/BSR20130065 Text en © 2013 The author(s) has paid for this article to be freely available under the terms of the Creative Commons Attribution Licence (CC-BY)(http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Review Article Silva, Jerson L. Rangel, Luciana P. Costa, Danielly C. F. Cordeiro, Yraima De Moura Gallo, Claudia V. Expanding the prion concept to cancer biology: dominant-negative effect of aggregates of mutant p53 tumour suppressor |
title | Expanding the prion concept to cancer biology: dominant-negative effect of aggregates of mutant p53 tumour suppressor |
title_full | Expanding the prion concept to cancer biology: dominant-negative effect of aggregates of mutant p53 tumour suppressor |
title_fullStr | Expanding the prion concept to cancer biology: dominant-negative effect of aggregates of mutant p53 tumour suppressor |
title_full_unstemmed | Expanding the prion concept to cancer biology: dominant-negative effect of aggregates of mutant p53 tumour suppressor |
title_short | Expanding the prion concept to cancer biology: dominant-negative effect of aggregates of mutant p53 tumour suppressor |
title_sort | expanding the prion concept to cancer biology: dominant-negative effect of aggregates of mutant p53 tumour suppressor |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3728989/ https://www.ncbi.nlm.nih.gov/pubmed/24003888 http://dx.doi.org/10.1042/BSR20130065 |
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