C9orf140, a novel Axin1-interacting protein, mediates the negative feedback loop of Wnt/ß-catenin signaling.
Oncogene
; 37(22): 2992-3005, 2018 05.
Article
em En
| MEDLINE
| ID: mdl-29531269
ABSTRACT
Wnt/ß-catenin signaling activity is maintained in homeostasis by an expanding list of molecular determinants. However, the molecular components and the regulatory mechanisms involved in its fine-tuning remain to be determined. Here, we identified C9orf140, a tumor-specific protein, as a novel Axin1-interacting protein by tandem-affinity purification and mass spectrometry. We further showed that C9orf140 is a negative regulator of Wnt/ß-catenin signaling in cultured cells as well as in zebrafish embryos. It functions upstream of ß-catenin, outcompetes PP2A for binding to Axin1, influences the balance between phosphorylation and de-phosphorylation of ß-catenin, and ultimately compromises Wnt3A-induced ß-catenin accumulation. Interestingly, Wnt-induced C9orf140 expression via ß-catenin. We propose that C9orf140 mediates a negative feedback loop of Wnt/ß-catenin signaling by interacting with Axin1. Our results advance the current understanding of the exquisite control of Wnt/ß-catenin signaling cascade, and provide evidence of the new role of C9orf140.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Ciclo Celular
/
Proteína Axina
/
Via de Sinalização Wnt
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Oncogene
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China