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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...

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Autores principales: Silva, Jerson L., Rangel, Luciana P., Costa, Danielly C. F., Cordeiro, Yraima, De Moura Gallo, Claudia V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2013
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.
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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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