PIDD mediates NF-kappaB activation in response to DNA damage

Détails

ID Serval
serval:BIB_47DF59AFEB0A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
PIDD mediates NF-kappaB activation in response to DNA damage
Périodique
Cell
Auteur(s)
Janssens  S., Tinel  A., Lippens  S., Tschopp  J.
ISSN
0092-8674 (Print)
Statut éditorial
Publié
Date de publication
12/2005
Volume
123
Numéro
6
Pages
1079-92
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Dec 16
Résumé
Activation of NF-kappaB following genotoxic stress allows time for DNA-damage repair and ensures cell survival accounting for acquired chemoresistance, an impediment to effective cancer therapy. Despite this clinical relevance, little is known about pathways that enable genotoxic-stress-induced NF-kappaB induction. Previously, we reported a role for the p53-inducible death-domain-containing protein, PIDD, in caspase-2 activation and apoptosis in response to DNA damage. We now demonstrate that PIDD plays a critical role in DNA-damage-induced NF-kappaB activation. Upon genotoxic stress, a complex between PIDD, the kinase RIP1, and a component of the NF-kappaB-activating kinase complex, NEMO, is formed. PIDD expression enhances genotoxic-stress-induced NF-kappaB activation through augmented sumoylation and ubiquitination of NEMO. Depletion of PIDD and RIP1, but not caspase-2, abrogates DNA-damage-induced NEMO modification and NF-kappaB activation. We propose that PIDD acts as a molecular switch, controlling the balance between life and death upon DNA damage.
Mots-clé
Adaptor Proteins, Signal Transducing/genetics Binding, Competitive CRADD Signaling Adaptor Protein Carrier Proteins/genetics/metabolism/*physiology Caspase 2 Caspases/genetics/metabolism Cell Line, Tumor Cell Nucleus/drug effects/metabolism DNA/genetics/metabolism DNA Damage/*physiology Doxorubicin/pharmacology Etoposide/pharmacology Fatty Acids, Unsaturated/pharmacology Hela Cells Humans Hypotonic Solutions/pharmacology I-kappa B Kinase/metabolism I-kappa B Proteins/metabolism Jurkat Cells Models, Biological NF-kappa B/*metabolism Nuclear Pore Complex Proteins/genetics/metabolism Phosphorylation/drug effects Protein Binding Protein Transport/drug effects RNA, Small Interfering/genetics RNA-Binding Proteins/genetics/metabolism Small Ubiquitin-Related Modifier Proteins/metabolism Transfection Tumor Necrosis Factor-alpha/pharmacology Ubiquitin/metabolism X-Linked Inhibitor of Apoptosis Protein/metabolism bcl-X Protein/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 16:18
Dernière modification de la notice
08/05/2019 18:02
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