SUMOylation-dependent localization of IKKepsilon in PML nuclear bodies is essential for protection against DNA-damage-triggered cell death.
Mol Cell
; 37(4): 503-15, 2010 Feb 26.
Article
em En
| MEDLINE
| ID: mdl-20188669
ABSTRACT
The IKK-related kinase IKKepsilon contributes to the antiviral response and can function as an oncogene that is frequently amplified in breast cancer. Here we report on an additional role of IKKepsilon as a mediator protecting from DNA-damage-induced cell death. Genotoxic stress allows for kinase-dependent entry of IKKepsilon into the nucleus, where IKKepsilon-dependent PML phosphorylation is a prerequisite for retention of this kinase in PML nuclear bodies. Within these subnuclear structures IKKepsilon inducibly colocalizes with TOPORS, which functions as a SUMO E3 ligase mediating SUMOylation of IKKepsilon at lysine 231. SUMO modification of IKKepsilon is required to trigger phosphorylation of nuclear substrates including NF-kappaB p65, thereby contributing to the antiapoptotic function of NF-kappaB in response to DNA damage.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Dano ao DNA
/
Proteínas Nucleares
/
Núcleo Celular
/
Apoptose
/
Proteínas Supressoras de Tumor
/
Proteína SUMO-1
/
Quinase I-kappa B
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article