Oncogenic Gain of Function in Glioblastoma Is Linked to Mutant p53 Amyloid Oligomers.
Biophysics
Cancer
Protein Structure Aspects
Structural Biology
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
21 Feb 2020
21 Feb 2020
Historique:
received:
21
08
2019
revised:
20
11
2019
accepted:
02
01
2020
pubmed:
26
1
2020
medline:
26
1
2020
entrez:
26
1
2020
Statut:
ppublish
Résumé
Tumor-associated p53 mutations endow cells with malignant phenotypes, including chemoresistance. Amyloid-like oligomers of mutant p53 transform this tumor suppressor into an oncogene. However, the composition and distribution of mutant p53 oligomers are unknown and the mechanism involved in the conversion is sparse. Here, we report accumulation of a p53 mutant within amyloid-like p53 oligomers in glioblastoma-derived cells presenting a chemoresistant gain-of-function phenotype. Statistical analysis from fluorescence fluctuation spectroscopy, pressure-induced measurements, and thioflavin T kinetics demonstrates the distribution of oligomers larger than the active tetrameric form of p53 in the nuclei of living cells and the destabilization of native-drifted p53 species that become amyloid. Collectively, these results provide insights into the role of amyloid-like mutant p53 oligomers in the chemoresistance phenotype of malignant and invasive brain tumors and shed light on therapeutic options to avert cancer.
Identifiants
pubmed: 31981923
pii: S2589-0042(20)30003-1
doi: 10.1016/j.isci.2020.100820
pmc: PMC6976948
pii:
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100820Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare that they have no conflicts of interest with the contents of this article.
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