Fam83F induces p53 stabilisation and promotes its activity.
Journal
Cell death and differentiation
ISSN: 1476-5403
Titre abrégé: Cell Death Differ
Pays: England
ID NLM: 9437445
Informations de publication
Date de publication:
Oct 2019
Oct 2019
Historique:
received:
04
01
2018
accepted:
09
01
2019
revised:
07
01
2019
pubmed:
30
1
2019
medline:
29
9
2020
entrez:
30
1
2019
Statut:
ppublish
Résumé
p53 is one of the most important tumour suppressor proteins currently known. It is activated in response to DNA damage and this activation leads to proliferation arrest and cell death. The abundance and activity of p53 are tightly controlled and reductions in p53's activity can contribute to the development of cancer. Here, we show that Fam83F increases p53 protein levels by protein stabilisation. Fam83F interacts with p53 and decreases its ubiquitination and degradation. Fam83F is induced in response to DNA damage and its overexpression also increases p53 activity in cell culture experiments and in zebrafish embryos. Downregulation of Fam83F decreases transcription of p53 target genes in response to DNA damage and increases cell proliferation, identifying Fam83F as an important regulator of the DNA damage response. Overexpression of Fam83F also enhances migration of cells harbouring mutant p53 demonstrating that it can also activate mutant forms of p53.
Identifiants
pubmed: 30692643
doi: 10.1038/s41418-019-0281-1
pii: 10.1038/s41418-019-0281-1
pmc: PMC6748130
doi:
Substances chimiques
FAM83F protein, human
0
Intracellular Signaling Peptides and Proteins
0
Neoplasm Proteins
0
Tumor Suppressor Protein p53
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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