Pygopus and the Wnt signaling pathway: a diverse set of connections

Bioessays. 2008 May;30(5):448-56. doi: 10.1002/bies.20757.


Identification of Pygopus in Drosophila as a dedicated component of the Wg (fly homolog of mammalian Wnt) signaling cascade initiated many inquiries into the mechanism of its function. Surprisingly, the nearly exclusive role for Pygopus in Wg signal transduction in flies is not seen in mice, where Pygopus appears to have both Wnt-related and Wnt-independent functions. This review addresses the initial findings of Pygopus as a Wg/Wnt co-activator in light of recent data from both fly and mammalian studies. We compare and contrast the developmental phenotypes of pygopus mutants to those characterized for known Wg/Wnt transducers and explore the data regarding a role for mammalian Pygopus 2 in tumorigenesis. We further analyze the roles of the two conserved domains of Pygopus proteins in transcription, and propose a model for the molecular mechanism of Pygopus function in both Wg/Wnt signaling and Wnt-independent transcriptional regulation.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Chromatin Assembly and Disassembly
  • Drosophila / genetics
  • Drosophila / growth & development
  • Drosophila / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Evolution, Molecular
  • Female
  • Genes, Insect
  • Humans
  • Intracellular Signaling Peptides and Proteins / deficiency
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Mice
  • Mice, Knockout
  • Models, Biological
  • Molecular Sequence Data
  • Mutation
  • Neoplasms / etiology
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Phenotype
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Species Specificity
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism*
  • Wnt1 Protein
  • beta Catenin / metabolism


  • Adaptor Proteins, Signal Transducing
  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • Proto-Oncogene Proteins
  • Pygo1 protein, mouse
  • Trans-Activators
  • Wnt Proteins
  • Wnt1 Protein
  • beta Catenin
  • pygo protein, Drosophila
  • pygopus 2 protein, mouse
  • wg protein, Drosophila