Sumoylation is involved in β-catenin-dependent activation of Tcf-4

Hideki Yamamoto, Motomasa Ihara, Yoshiharu Matsuura, Akira Kikuchi

Research output: Contribution to journalArticlepeer-review

145 Citations (Scopus)


Sumoylation is involved in mediating protein - protein interactions, subcellular compartmentalization and protein stability. Our analysis of various Wnt signaling molecules revealed that one of them, Tcf-4, is sumoylated at the endogenous level. At least one sumoylation site, Lys297, of Tcf-4 was identified. The sumoylation of Tcf-4 was enhanced by PIASy, a SUMO E3 enzyme, and inhibited by Axam, a desumoylation enzyme. Although PIASy did not affect the interaction of Tcf-4 with β-catenin or DNA, Tcf-4, SUMO-1 and PIASy were co-localized in the nucleus and present in a complex in the PML body. PIASy enhanced β-catenin-dependent transcriptional activity of Tcf-4, whereas Axam inhibited it. Reduction of the protein level of Axam by RNA interference led to an increase in sumoylation of Tcf-4 and activation of Tcf-4. Furthermore, β-catenin and PIASy activated Tcf-4K297R, in which Lys297 was changed to arginine, less than wild-type Tcf-4. These results suggest that sumoylation of Tcf-4 is involved in β-catenin-dependent and Tcf-4-mediated gene expression in the Wnt signaling pathway.

Original languageEnglish
Pages (from-to)2047-2059
Number of pages13
JournalEMBO Journal
Issue number9
Publication statusPublished - 2003 May 1
Externally publishedYes


  • Axam
  • Gene expression
  • PIAS
  • Sumoylation
  • Tcf-4

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)


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