C9orf140, a novel Axin1-interacting protein, mediates the negative feedback loop of Wnt/?-catenin signaling.

ABSTRACT: Wnt/?-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/?-catenin signaling in cultured cells as well as in zebrafish embryos. It functions upstream of ?-catenin, outcompetes PP2A for binding to Axin1, influences the balance between phosphorylation and de-phosphorylation of ?-catenin, and ultimately compromises Wnt3A-induced ?-catenin accumulation. Interestingly, Wnt-induced C9orf140 expression via ?-catenin. We propose that C9orf140 mediates a negative feedback loop of Wnt/?-catenin signaling by interacting with Axin1. Our results advance the current understanding of the exquisite control of Wnt/?-catenin signaling cascade, and provide evidence of the new role of C9orf140.

SUBMITTER: Jiang J 

PROVIDER: S-EPMC5978805 | biostudies-other | 2018 May

REPOSITORIES: biostudies-other