p53-induced protein with a death domain (PIDD) isoforms differentially activate nuclear factor-kappaB and caspase-2 in response to genotoxic stress

Détails

ID Serval
serval:BIB_8F27D2A521E4
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
p53-induced protein with a death domain (PIDD) isoforms differentially activate nuclear factor-kappaB and caspase-2 in response to genotoxic stress
Périodique
Oncogene
Auteur(s)
Cuenin S., Tinel A., Janssens S., Tschopp J.
ISSN
1476-5594
Statut éditorial
Publié
Date de publication
2008
Peer-reviewed
Oui
Volume
27
Numéro
3
Pages
387-396
Langue
anglais
Résumé
Cells respond to DNA damage in a complex way and the fate of damaged cells depends on the balance between pro- and antiapoptotic signals. This is of crucial importance in cancer as genotoxic stress is implied both in oncogenesis and in classical tumor therapies. p53-induced protein with a death domain (PIDD), initially described as a p53-inducible gene, is one of the molecular switches able to activate a survival or apoptotic program. Two isoforms of PIDD, PIDD (isoform 1) and LRDD (isoform 2), have already been reported and we describe here a third isoform. These three isoforms are differentially expressed in tissues and cell lines. Genotoxic stress only affects PIDD isoform 3 mRNA levels, whereas isoforms 1 and 2 mRNA levels remain unchanged. All isoforms are capable of activating nuclear factor-kappaB in response to genotoxic stress, but only isoform 1 interacts with RIP-associated ICH-1/CED-3 homologous protein with a death domain and activates caspase-2. Isoform 2 counteracts the pro-apoptotic function of isoform 1, whereas isoform 3 enhances it. Thus, the differential splicing of PIDD mRNA leads to the formation of at least three proteins with antagonizing/agonizing functions, thereby regulating cell fate in response to DNA damage
Mots-clé
Affect , Biochemistry , Carrier Proteins , Caspase 2 , Cell Line , Dna , DNA Damage , genetics , Humans , metabolism , NF-kappa B , Protein Isoforms , Proteins , RNA Splicing , Survival , Switzerland , therapy , Tumor Suppressor Protein p53 , Universities
Pubmed
Web of science
Création de la notice
29/01/2009 23:14
Dernière modification de la notice
03/03/2018 19:20
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