Structural basis of Keap1 interactions with Nrf2.
Free Radic Biol Med
; 88(Pt B): 101-107, 2015 Nov.
Article
en En
| MEDLINE
| ID: mdl-26057936
ABSTRACT
Keap1 is a highly redox-sensitive member of the BTB-Kelch family that assembles with the Cul3 protein to form a Cullin-RING E3 ligase complex for the degradation of Nrf2. Oxidative stress disables Keap1, allowing Nrf2 protein levels to accumulate for the transactivation of critical stress response genes. Consequently, the Keap1-Nrf2 system is extensively pursued for the development of protein-protein interaction inhibitors that will stabilize Nrf2 for therapeutic effect in conditions of neurodegeneration, inflammation, and cancer. Here we review current progress toward the structure determination of Keap1 and its protein complexes with Cul3, Nrf2 substrate, and small-molecule antagonists. Together the available structures establish a rational three-dimensional model to explain the two-site binding of Nrf2 as well as its efficient ubiquitination.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Modelos Moleculares
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Estrés Oxidativo
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Péptidos y Proteínas de Señalización Intracelular
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Factor 2 Relacionado con NF-E2
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Free Radic Biol Med
Asunto de la revista:
BIOQUIMICA
/
MEDICINA
Año:
2015
Tipo del documento:
Article