ZFIN ID: ZDB-PUB-180314-5
C9orf140, a novel Axin1-interacting protein, mediates the negative feedback loop of Wnt/β-catenin signaling
Jiang, J., Tang, S., Xia, J., Wen, J., Chen, S., Shu, X., Huen, M.S.Y., Deng, Y.
Date: 2018
Source: Oncogene   37(22): 2992-3005 (Journal)
Registered Authors:
Keywords: none
MeSH Terms:
  • Animals
  • Axin Protein/metabolism*
  • Binding Sites
  • Cell Cycle Proteins/chemistry*
  • Cell Cycle Proteins/metabolism*
  • Feedback, Physiological
  • HEK293 Cells
  • HeLa Cells
  • Hep G2 Cells
  • Humans
  • MCF-7 Cells
  • Mass Spectrometry
  • Phosphorylation
  • Protein Phosphatase 2/metabolism
  • Tandem Affinity Purification
  • Wnt Signaling Pathway*
  • Wnt3A Protein/metabolism
  • Zebrafish/embryology
  • Zebrafish/metabolism
  • beta Catenin/metabolism
PubMed: 29531269 Full text @ Oncogene
Wnt/β-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/β-catenin signaling in cultured cells as well as in zebrafish embryos. It functions upstream of β-catenin, outcompetes PP2A for binding to Axin1, influences the balance between phosphorylation and de-phosphorylation of β-catenin, and ultimately compromises Wnt3A-induced β-catenin accumulation. Interestingly, Wnt-induced C9orf140 expression via β-catenin. We propose that C9orf140 mediates a negative feedback loop of Wnt/β-catenin signaling by interacting with Axin1. Our results advance the current understanding of the exquisite control of Wnt/β-catenin signaling cascade, and provide evidence of the new role of C9orf140.