Chibby cooperates with 14-3-3 to regulate beta-catenin subcellular distribution and signaling activity

J Cell Biol. 2008 Jun 30;181(7):1141-54. doi: 10.1083/jcb.200709091. Epub 2008 Jun 23.


beta-Catenin functions in both cell-cell adhesion and as a transcriptional coactivator in the canonical Wnt pathway. Nuclear accumulation of beta-catenin is the hallmark of active Wnt signaling and is frequently observed in human cancers. Although beta-catenin shuttles in and out of the nucleus, the molecular mechanisms underlying its translocation remain poorly understood. Chibby (Cby) is an evolutionarily conserved molecule that inhibits beta-catenin-mediated transcriptional activation. Here, we identified 14-3-3epsilon and 14-3-3zeta as Cby-binding partners using affinity purification/mass spectrometry. 14-3-3 proteins specifically recognize serine 20 within the 14-3-3-binding motif of Cby when phosphorylated by Akt kinase. Notably, 14-3-3 binding results in sequestration of Cby into the cytoplasm. Moreover, Cby and 14-3-3 form a stable tripartite complex with beta-catenin, causing beta-catenin to partition into the cytoplasm. Our results therefore suggest a novel paradigm through which Cby acts in concert with 14-3-3 proteins to facilitate nuclear export of beta-catenin, thereby antagonizing beta-catenin signaling.

Publication types

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

MeSH terms

  • 14-3-3 Proteins / metabolism*
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • COS Cells
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • Cell Nucleus / enzymology
  • Chlorocebus aethiops
  • Humans
  • Models, Biological
  • Molecular Sequence Data
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*
  • Phosphorylation
  • Protein Binding
  • Protein Isoforms / metabolism
  • Protein Transport
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction*
  • Subcellular Fractions / metabolism
  • Substrate Specificity
  • Transcriptional Activation
  • beta Catenin / metabolism*


  • 14-3-3 Proteins
  • CBY1 protein, human
  • Carrier Proteins
  • Nuclear Proteins
  • Protein Isoforms
  • beta Catenin
  • Proto-Oncogene Proteins c-akt