Please use this identifier to cite or link to this item:
Title: The tumor suppressor CYLD regulates the p53 DNA damage response
Author: Fernández-Majada, Vanesa
Welz, Patrick-Simon
Ermolaeva, Maria
Schell, Michael
Adam, Alexander
Dietlein, Felix
Komander, David
Büttner, Reinhard
Thomas, Roman K.
Schumacher, Björn
Pasparakis, Manolis
Keywords: Apoptosi
Experimentació animal
Animal experimentation
Issue Date: 2016
Publisher: Nature Publishing Group
Abstract: The tumour suppressor CYLD is a deubiquitinase previously shown to inhibit NF-κB, MAP kinase and Wnt signalling. However, the tumour suppressing mechanisms of CYLD remain poorly understood. Here we show that loss of CYLD catalytic activity causes impaired DNA damage-induced p53 stabilization and activation in epithelial cells and sensitizes mice to chemical carcinogen-induced intestinal and skin tumorigenesis. Mechanistically, CYLD interacts with and deubiquitinates p53 facilitating its stabilization in response to genotoxic stress. Ubiquitin chain-restriction analysis provides evidence that CYLD removes K48 ubiquitin chains from p53 indirectly by cleaving K63 linkages, suggesting that p53 is decorated with complex K48/K63 chains. Moreover, CYLD deficiency also diminishes CEP-1/p53-dependent DNA damage-induced germ cell apoptosis in the nematode Caenorhabditis elegans. Collectively, our results identify CYLD as a deubiquitinase facilitating DNA damage-induced p53 activation and suggest that regulation of p53 responses to genotoxic stress contributes to the tumour suppressor function of CYLD.
Note: Reproducció del document publicat a:
It is part of: Nature Communications, 2016, vol. 7
Related resource:
ISSN: 2041-1723
Appears in Collections:Articles publicats en revistes (Patologia i Terapèutica Experimental)

Files in This Item:
File Description SizeFormat 
700997.pdf1.58 MBAdobe PDFView/Open

This item is licensed under a Creative Commons License Creative Commons