Sestrin 2 protein regulates platelet-derived growth factor receptor ß (Pdgfrß) expression by modulating proteasomal and Nrf2 transcription factor functions.
J Biol Chem
; 290(15): 9738-52, 2015 Apr 10.
Article
em En
| MEDLINE
| ID: mdl-25716320
ABSTRACT
We recently identified the antioxidant protein Sestrin 2 (Sesn2) as a suppressor of platelet-derived growth factor receptor ß (Pdgfrß) signaling and Pdgfrß signaling as an inducer of lung regeneration and injury repair. Here, we identified Sesn2 and the antioxidant gene inducer nuclear factor erythroid 2-related factor 2 (Nrf2) as positive regulators of proteasomal function. Inactivation of Sesn2 or Nrf2 induced reactive oxygen species-mediated proteasomal inhibition and Pdgfrß accumulation. Using bacterial artificial chromosome (BAC) transgenic HeLa and mouse embryonic stem cells stably expressing enhanced green fluorescent protein-tagged Sesn2 at nearly endogenous levels, we also showed that Sesn2 physically interacts with 2-Cys peroxiredoxins and Nrf2 albeit under different reductive conditions. Overall, we characterized a novel, redox-sensitive Sesn2/Pdgfrß suppressor pathway that negatively interferes with lung regeneration and is up-regulated in the emphysematous lungs of patients with chronic obstructive pulmonary disease (COPD).
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Nucleares
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Receptor beta de Fator de Crescimento Derivado de Plaquetas
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Complexo de Endopeptidases do Proteassoma
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Fator 2 Relacionado a NF-E2
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Alemanha