The nonredundant nature of the Axin2 regulatory network in the canonical Wnt signaling pathway

Proc Natl Acad Sci U S A. 2022 Mar 1;119(9):e2108408119. doi: 10.1073/pnas.2108408119.


Axin is one of two essential scaffolds in the canonical Wnt pathway that converts signals at the plasma membrane to signals inhibiting the degradation of β-catenin, leading to its accumulation and specific gene activation. In vertebrates, there are two forms of Axin, Axin1 and Axin2, which are similar at the protein level and genetically redundant. We show here that differential regulation of the two genes on the transcriptional and proteostatic level confers differential responsiveness that can be used in tissue-specific regulation. Such subtle features may distinguish other redundant gene pairs that are commonly found in vertebrates through gene knockout experiments.

Keywords: Axin; Wnt; feedback regulation; genetic redundancy.

MeSH terms

  • Axin Protein / genetics
  • Axin Protein / metabolism*
  • Cell Line
  • Humans
  • Proteostasis
  • Transcription, Genetic / physiology
  • Wnt Signaling Pathway*
  • Wnt3A Protein / metabolism
  • beta Catenin / metabolism


  • AXIN2 protein, human
  • Axin Protein
  • CTNNB1 protein, human
  • Wnt3A Protein
  • beta Catenin