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Cell Death Differ. 2019 Jan 28. doi: 10.1038/s41418-019-0281-1. [Epub ahead of print]

Fam83F induces p53 stabilisation and promotes its activity.

Author information

1
Karlsruhe Institute of Technology, Institute of Toxicology and Genetics, PO-box 3640, 76021, Karlsruhe, Germany.
2
Histochemistry and Cell Biology Department, Medical Research Institute, Alexandria University, 165 Horreya Avenue, Hadara, Alexandria, Egypt.
3
Human Physiology Department, Medical Research Institute, Alexandria University, 165 Horreya Avenue, Hadara, Alexandria, Egypt.
4
Faculty of Medicine, University of Valparaiso, Valparaiso, Chile.
5
Ludwig Institute for Cancer Research, University of Oxford, Oxford, OX3 7DQ, UK.
6
Klinik fuer Allgemeine Chirurgie, Universitaetsklinikum des Saarlandes, Kirrberger Str., 66421, Homburg, Germany.
7
Department of Cellular, Computational and Integratrive Biology (CIBIO), University of Trento, Via Sommarive 9, Trento, Italy.
8
Department of Cellular Pathology, Clarence Wing, St. Mary's Campus, London, UK.
9
Sorbonne Université, UPMC Univ Paris 06, F-75005, Paris, France.
10
Department of Oncology-Pathology, Cancer Center Karolinska (CCK), Karolinska Institutet, Stockholm, Sweden.
11
INSERM, U1138, Équipe 11, Centre de Recherche des Cordeliers, Paris, France.
12
Karlsruhe Institute of Technology, Institute of Toxicology and Genetics, PO-box 3640, 76021, Karlsruhe, Germany. christine.blattner@kit.edu.

Abstract

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.

PMID:
30692643
DOI:
10.1038/s41418-019-0281-1

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