Complexes formed by mutant p53 and their roles in breast cancer

Arianna Bellazzo,1 Daria Sicari,1,2 Elena Valentino,1,2 Giannino Del Sal,1,2 Licio Collavin1,2 1National Laboratory CIB (LNCIB), AREA Science park, Trieste, Italy; 2Department of Life Sciences, University of Trieste, Trieste, ItalyAbstract: Breast cancer is the most frequently diagnosed mal...

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Autores principales:	Bellazzo A, Sicari D, Valentino E, Del Sal G, Collavin L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	protein-protein interactions mutant p53 gain-of-function targeted therapy cancer cell homeostasis. Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/88b7b2901eab41f88ffff9a1252b92f3
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spelling	oai:doaj.org-article:88b7b2901eab41f88ffff9a1252b92f32021-12-02T02:40:44ZComplexes formed by mutant p53 and their roles in breast cancer1179-1314https://doaj.org/article/88b7b2901eab41f88ffff9a1252b92f32018-06-01T00:00:00Zhttps://www.dovepress.com/complexes-formed-by-mutant-p53-and-their-roles-in-breast-cancer-peer-reviewed-article-BCTThttps://doaj.org/toc/1179-1314Arianna Bellazzo,1 Daria Sicari,1,2 Elena Valentino,1,2 Giannino Del Sal,1,2 Licio Collavin1,2 1National Laboratory CIB (LNCIB), AREA Science park, Trieste, Italy; 2Department of Life Sciences, University of Trieste, Trieste, ItalyAbstract: Breast cancer is the most frequently diagnosed malignancy in women, and mutations in the tumor suppressor p53 are commonly detected in the most aggressive subtypes. The majority of TP53 gene alterations are missense substitutions, leading to expression of mutant forms of the p53 protein that are frequently detected at high levels in cancer cells. P53 mutants not only lose the physiological tumor-suppressive activity of the wild-type p53 protein but also acquire novel powerful oncogenic functions, referred to as gain of function, that may actively confer a selective advantage during tumor progression. Some of the best-characterized oncogenic activities of mutant p53 are mediated by its ability to form aberrant protein complexes with other transcription factors or proteins not directly related to gene transcription. The set of cellular proteins available to interact with mutant p53 is dependent on cell type and extensively affected by environmental signals, so the prognostic impact of p53 mutation is complex. Specific functional interactions of mutant p53 can profoundly impact homeostasis of breast cancer cells, reprogramming gene expression in response to specific extracellular inputs or cell-intrinsic conditions. The list of protein complexes involving mutant p53 in breast cancer is continuously growing, as is the number of oncogenic phenotypes in which they could be involved. In consideration of the functional impact of such complexes, key interactions of mutant p53 may be exploited as potential targets for development of therapies aimed at defusing the oncogenic potential of p53 mutation. Keywords: protein–protein interactions, mutant p53 gain of function, targeted therapy, cancer-cell homeostasisBellazzo ASicari DValentino EDel Sal GCollavin LDove Medical Pressarticleprotein-protein interactionsmutant p53 gain-of-functiontargeted therapycancer cell homeostasis.Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBreast Cancer: Targets and Therapy, Vol Volume 10, Pp 101-112 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	protein-protein interactions mutant p53 gain-of-function targeted therapy cancer cell homeostasis. Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	protein-protein interactions mutant p53 gain-of-function targeted therapy cancer cell homeostasis. Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Bellazzo A Sicari D Valentino E Del Sal G Collavin L Complexes formed by mutant p53 and their roles in breast cancer
description	Arianna Bellazzo,1 Daria Sicari,1,2 Elena Valentino,1,2 Giannino Del Sal,1,2 Licio Collavin1,2 1National Laboratory CIB (LNCIB), AREA Science park, Trieste, Italy; 2Department of Life Sciences, University of Trieste, Trieste, ItalyAbstract: Breast cancer is the most frequently diagnosed malignancy in women, and mutations in the tumor suppressor p53 are commonly detected in the most aggressive subtypes. The majority of TP53 gene alterations are missense substitutions, leading to expression of mutant forms of the p53 protein that are frequently detected at high levels in cancer cells. P53 mutants not only lose the physiological tumor-suppressive activity of the wild-type p53 protein but also acquire novel powerful oncogenic functions, referred to as gain of function, that may actively confer a selective advantage during tumor progression. Some of the best-characterized oncogenic activities of mutant p53 are mediated by its ability to form aberrant protein complexes with other transcription factors or proteins not directly related to gene transcription. The set of cellular proteins available to interact with mutant p53 is dependent on cell type and extensively affected by environmental signals, so the prognostic impact of p53 mutation is complex. Specific functional interactions of mutant p53 can profoundly impact homeostasis of breast cancer cells, reprogramming gene expression in response to specific extracellular inputs or cell-intrinsic conditions. The list of protein complexes involving mutant p53 in breast cancer is continuously growing, as is the number of oncogenic phenotypes in which they could be involved. In consideration of the functional impact of such complexes, key interactions of mutant p53 may be exploited as potential targets for development of therapies aimed at defusing the oncogenic potential of p53 mutation. Keywords: protein–protein interactions, mutant p53 gain of function, targeted therapy, cancer-cell homeostasis
format	article
author	Bellazzo A Sicari D Valentino E Del Sal G Collavin L
author_facet	Bellazzo A Sicari D Valentino E Del Sal G Collavin L
author_sort	Bellazzo A
title	Complexes formed by mutant p53 and their roles in breast cancer
title_short	Complexes formed by mutant p53 and their roles in breast cancer
title_full	Complexes formed by mutant p53 and their roles in breast cancer
title_fullStr	Complexes formed by mutant p53 and their roles in breast cancer
title_full_unstemmed	Complexes formed by mutant p53 and their roles in breast cancer
title_sort	complexes formed by mutant p53 and their roles in breast cancer
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/88b7b2901eab41f88ffff9a1252b92f3
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Complexes formed by mutant p53 and their roles in breast cancer

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