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

Authors :
Y. Matsuura
A. Kikuchi
H. Yamamoto
M. Ihara
Source :
EMBO Journal; 5/1/2003, Vol. 22 Issue 9, p2047-2059, 13p
Publication Year :
2003

Abstract

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-4<superscript>K297R</superscript>, 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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
02614189
Volume :
22
Issue :
9
Database :
Complementary Index
Journal :
EMBO Journal
Publication Type :
Academic Journal
Accession number :
10399905