Tumor suppressor p53: from engaging DNA to target gene regulation.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
18 09 2020
18 09 2020
Historique:
accepted:
30
07
2020
revised:
24
07
2020
received:
24
05
2020
pubmed:
17
8
2020
medline:
29
10
2020
entrez:
16
8
2020
Statut:
ppublish
Résumé
The p53 transcription factor confers its potent tumor suppressor functions primarily through the regulation of a large network of target genes. The recent explosion of next generation sequencing protocols has enabled the study of the p53 gene regulatory network (GRN) and underlying mechanisms at an unprecedented depth and scale, helping us to understand precisely how p53 controls gene regulation. Here, we discuss our current understanding of where and how p53 binds to DNA and chromatin, its pioneer-like role, and how this affects gene regulation. We provide an overview of the p53 GRN and the direct and indirect mechanisms through which p53 affects gene regulation. In particular, we focus on delineating the ubiquitous and cell type-specific network of regulatory elements that p53 engages; reviewing our understanding of how, where, and when p53 binds to DNA and the mechanisms through which these events regulate transcription. Finally, we discuss the evolution of the p53 GRN and how recent work has revealed remarkable differences between vertebrates, which are of particular importance to cancer researchers using mouse models.
Identifiants
pubmed: 32797160
pii: 5892750
doi: 10.1093/nar/gkaa666
pmc: PMC7498329
doi:
Substances chimiques
Chromatin
0
TP53 protein, human
0
Tumor Suppressor Protein p53
0
DNA
9007-49-2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
8848-8869Subventions
Organisme : Wellcome Trust
ID : 110371/Z/15/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S021205/1
Pays : United Kingdom
Organisme : NIGMS NIH HHS
ID : R15 GM128049
Pays : United States
Organisme : Cancer Research UK
ID : 24387
Pays : United Kingdom
Organisme : Intramural NIH HHS
ID : Z01 ES100557
Pays : United States
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/T002824/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0400302
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C11884/A24367
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_17117
Pays : United Kingdom
Organisme : Intramural NIH HHS
ID : Z01 ES065079
Pays : United States
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.
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