NF-kappaB activation by combinations of NEMO SUMOylation and ATM activation stresses in the absence of DNA damage.
Oncogene
; 26(5): 641-51, 2007 Feb 01.
Article
en En
| MEDLINE
| ID: mdl-16862178
The inactive transcription factor NF-kappaB is localized in the cytoplasm and rapidly responds to a variety of extracellular factors and intracellular stress conditions to initiate multiple cellular responses. While the knowledge regarding NF-kappaB signaling pathways initiated by extracellular ligands is rapidly expanding, the mechanisms of activation by intracellular stress conditions are not well understood. We recently described a critical role for a small ubiquitin-like modifier (SUMO) modification of NF-kappaB essential modulator (NEMO), the regulatory subunit of the IkappaB kinase, in response to certain genotoxic stress conditions. One important unanswered question is whether the role of this modification is limited to the genotoxic agents or some other signaling pathways also employ SUMOylation of NEMO to regulate NF-kappaB activation. Here, we report that a variety of other stress conditions, including oxidative stress, ethanol exposure, heat shock and electric shock, also induce NEMO SUMOylation, thus demonstrating that DNA damage per se is not necessary for this NEMO modification to occur. Moreover, combinations of certain SUMO stress and ATM (ataxia telangiectasia mutated) activation conditions lead to NF-kappaB activation without inducing DNA damage. Our study helps to conceptualize how individual or a combination of different stress conditions may funnel into this previously unappreciated signal transduction mechanism to regulate the activity of the ubiquitous NF-kappaB transcription factor.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Daño del ADN
/
FN-kappa B
/
Proteínas Serina-Treonina Quinasas
/
Proteínas de Ciclo Celular
/
Proteínas Supresoras de Tumor
/
Proteína SUMO-1
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Péptidos y Proteínas de Señalización Intracelular
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Proteínas de Unión al ADN
Límite:
Animals
Idioma:
En
Revista:
Oncogene
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido