Sumoylation is involved in beta-catenin-dependent activation of Tcf-4.
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 beta-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 beta-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, beta-catenin and PIASy activated Tcf-4(K297R), in which Lys297 was changed to arginine, less than wild-type Tcf-4. These results suggest that sumoylation of Tcf-4 is involved in beta-catenin-dependent and Tcf-4-mediated gene expression in the Wnt signaling pathway.
Department of Biochemistry, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Hideki
H
Yamamoto
Motomasa
M
Ihara
Yoshiharu
Y
Matsuura
Akira
A
Kikuchi
D000818:Animals; D019556:COS Cells; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D005455:Fluorescent Antibody Technique; D011485:Protein Binding; D025842:SUMO-1 Protein / Q000378:metabolism*; D051820:TCF Transcription Factors; D015534:Trans-Activators / Q000378:metabolism*; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors / Q000378:metabolism*; D051176:beta Catenin
D003598:Cytoskeletal Proteins; D025842:SUMO-1 Protein; D051820:TCF Transcription Factors; D015534:Trans-Activators; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors; D051176:beta Catenin; D004247:DNA