A role for bioinorganic chemistry in the reactivation of mutant p53 in cancer.
Anticancer agents
Metallochaperones
Mutant protein reactivation
Journal
Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry
ISSN: 1432-1327
Titre abrégé: J Biol Inorg Chem
Pays: Germany
ID NLM: 9616326
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
received:
07
03
2022
accepted:
11
04
2022
pubmed:
1
5
2022
medline:
26
8
2022
entrez:
30
4
2022
Statut:
ppublish
Résumé
Metal ion dysregulation has been implicated in a number of diseases from neurodegeneration to cancer. While defective metal ion transport mechanisms are known to cause specific diseases of genetic origin, the role of metal dysregulation in many diseases has yet to be elucidated due to the complicated function (both good and bad!) of metal ions in the body. A breakdown in metal ion speciation can manifest in several ways from increased reactive oxygen species (ROS) generation to an increase in protein misfolding and aggregation. In this review, we will discuss the role of Zn in the proper function of the p53 protein in cancer. The p53 protein plays a critical role in the prevention of genome mutations via initiation of apoptosis, DNA repair, cell cycle arrest, anti-angiogenesis, and senescence pathways to avoid propagation of damaged cells. p53 is the most frequently mutated protein in cancer and almost all cancers exhibit malfunction along the p53 pathway. Thus, there has been considerable effort dedicated to restoring normal p53 expression and activity to mutant p53. This includes understanding the relative populations of the Zn-bound and Zn-free p53 in wild-type and mutant forms, and the development of metallochaperones to re-populate the Zn binding site to restore mutant p53 activity. Parallels will be made to the development of multifunctional metal binding agents for modulating the aggregation of the amyloid-beta peptide in Alzheimer's Disease (AD).
Identifiants
pubmed: 35488931
doi: 10.1007/s00775-022-01939-2
pii: 10.1007/s00775-022-01939-2
doi:
Substances chimiques
Metallochaperones
0
Metals
0
Tumor Suppressor Protein p53
0
Zinc
J41CSQ7QDS
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
393-403Subventions
Organisme : Natural Sciences and Engineering Research Council of Canada
ID : RGPIN-2019-06749
Informations de copyright
© 2022. The Author(s), under exclusive licence to Society for Biological Inorganic Chemistry (SBIC).
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