Targeting cellular senescence in cancer and aging: roles of p53 and its isoforms.
Aging
Alternative Splicing
Animals
Antineoplastic Agents
/ pharmacology
Apoptosis
/ drug effects
Carcinogenesis
/ drug effects
Cellular Reprogramming
/ drug effects
Cellular Senescence
/ drug effects
DNA Repair
/ drug effects
Humans
Neoplasms
/ drug therapy
Neurodegenerative Diseases
/ etiology
Protein Isoforms
/ genetics
Tumor Suppressor Protein p53
/ genetics
Journal
Carcinogenesis
ISSN: 1460-2180
Titre abrégé: Carcinogenesis
Pays: England
ID NLM: 8008055
Informations de publication
Date de publication:
12 08 2020
12 08 2020
Historique:
received:
18
05
2020
revised:
26
06
2020
accepted:
29
06
2020
pubmed:
4
7
2020
medline:
10
6
2021
entrez:
4
7
2020
Statut:
ppublish
Résumé
Cellular senescence and the associated secretory phenotype (SASP) promote disease in the aged population. Targeting senescent cells by means of removal, modulation of SASP or through cellular reprogramming represents a novel therapeutic avenue for treating cancer- and age-related diseases such as neurodegeneration, pulmonary fibrosis and renal disease. Cellular senescence is partly regulated by the TP53 gene, a critical tumor suppressor gene which encodes 12 or more p53 protein isoforms. This review marks a significant milestone of 40 years of Carcinogenesis publication history and p53 research and 15 years of p53 isoform research. The p53 isoforms are produced through initiation at alternative transcriptional and translational start sites and alternative mRNA splicing. These truncated p53 isoform proteins are endogenously expressed in normal human cells and maintain important functional roles, including modulation of full-length p53-mediated cellular senescence, apoptosis and DNA repair. In this review, we discuss the mechanisms and functions of cellular senescence and SASP in health and disease, the regulation of cellular senescence by p53 isoforms, and the therapeutic potential of targeting cellular senescence to treat cancer- and age-associated diseases.
Identifiants
pubmed: 32619002
pii: 5867012
doi: 10.1093/carcin/bgaa071
pmc: PMC7422622
doi:
Substances chimiques
Antineoplastic Agents
0
Protein Isoforms
0
TP53 protein, human
0
Tumor Suppressor Protein p53
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1017-1029Informations de copyright
Published by Oxford University Press 2020.
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