ß-TrCP1 Is a Vacillatory Regulator of Wnt Signaling.
Cell Chem Biol
; 24(8): 944-957.e7, 2017 Aug 17.
Article
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| MEDLINE
| ID: mdl-28736239
Simultaneous hyperactivation of Wnt and antioxidant response (AR) are often observed during oncogenesis. However, it remains unclear how the ß-catenin-driven Wnt and the Nrf2-driven AR mutually regulate each other. The situation is compounded because many players in these two pathways are redox sensors, rendering bolus redox signal-dosing methods uninformative. Herein we examine the ramifications of single-protein target-specific AR upregulation in various knockdown lines. Our data document that Nrf2/AR strongly inhibits ß-catenin/Wnt. The magnitude and mechanism of this negative regulation are dependent on the direct interaction between ß-catenin N terminus and ß-TrCP1 (an antagonist of both Nrf2 and ß-catenin), and independent of binding between Nrf2 and ß-TrCP1. Intriguingly, ß-catenin positively regulates AR. Because AR is a negative regulator of Wnt regardless of ß-catenin N terminus, this switch of function is likely sufficient to establish a new Wnt/AR equilibrium during tumorigenesis.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas con Repetición de beta-Transducina
/
Proteínas Wnt
Límite:
Humans
Idioma:
En
Revista:
Cell Chem Biol
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos