E3 ligase STUB1/CHIP regulates NAD(P)H:quinone oxidoreductase 1 (NQO1) accumulation in aged brain, a process impaired in certain Alzheimer disease patients.
J Biol Chem
; 286(11): 8839-45, 2011 Mar 18.
Article
en En
| MEDLINE
| ID: mdl-21220432
ABSTRACT
NAD(P)Hquinone oxidoreductase 1 (NQO1) is a flavoenzyme that is important in maintaining the cellular redox state and regulating protein degradation. The NQO1 polymorphism C609T has been associated with increased susceptibility to various age-related pathologies. We show here that NQO1 protein level is regulated by the E3 ligase STUB1/CHIP (C terminus of Hsc70-interacting protein). NQO1 binds STUB1 via the Hsc70-interacting domain (tetratricopeptide repeat domain) and undergoes ubiquitination and degradation. We demonstrate here that the product of the C609T polymorphism (P187S) is a stronger STUB1 interactor with increased susceptibility to ubiquitination by the E3 ligase STUB1. Furthermore, age-dependent decrease of STUB1 correlates with increased NQO1 accumulation. Remarkably, examination of hippocampi from Alzheimer disease patients revealed that in half of the cases examined the NQO1 protein level was undetectable due to C609T polymorphism, suggesting that the age-dependent accumulation of NQO1 is impaired in certain Alzheimer disease patients.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Envejecimiento
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NAD(P)H Deshidrogenasa (Quinona)
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Ubiquitina-Proteína Ligasas
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Enfermedad de Alzheimer
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Hipocampo
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Proteínas del Tejido Nervioso
Límite:
Humans
Idioma:
En
Año:
2011
Tipo del documento:
Article