A beta-catenin identified by functional rather than sequence criteria and its role in Wnt/MAPK signaling

Cell. 2005 Jun 3;121(5):761-72. doi: 10.1016/j.cell.2005.03.029.


Wnt/MAPK signaling is a common variant of Wnt signaling in C. elegans and has been implicated in vertebrates. The sys-1 gene works with Wnt/MAPK signaling to control cell fates during C. elegans development. We report that the SYS-1 amino acid sequence is novel but that SYS-1 functions as beta-catenin: SYS-1 rescues a bar-1/beta-catenin null mutant, binds the POP-1/TCF beta-catenin binding domain, and coactivates POP-1-dependent transcription. Moreover, we provide genetic and molecular evidence that SYS-1 levels are crucial to POP-1 activity. Our results suggest that Wnt/MAPK signaling promotes POP-1 export from the nucleus to accommodate the limiting availability of its SYS-1/beta-catenin transcriptional coactivator. Discovery of SYS-1/beta-catenin extends our definition of beta-catenins and brings together aspects of the canonical mechanism for Wnt signaling with the noncanonical Wnt/MAPK mechanism. We discuss the idea that a similar pathway may be employed broadly in animal development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • DNA-Binding Proteins / metabolism
  • High Mobility Group Proteins / metabolism
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Mitogen-Activated Protein Kinases / metabolism*
  • Signal Transduction / physiology*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Wnt Proteins


  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • High Mobility Group Proteins
  • Intercellular Signaling Peptides and Proteins
  • Sys-1 protein, C elegans
  • Trans-Activators
  • Transcription Factors
  • Wnt Proteins
  • pop-1 protein, C elegans
  • Mitogen-Activated Protein Kinases