Back to Search Start Over

SUMOylation target sites at the C terminus protect Axin from ubiquitination and confer protein stability

SUMOylation target sites at the C terminus protect Axin from ubiquitination and confer protein stability

Authors :
Frank Costantini
Ian V. Chia
Min Jung Kim
Source :
The FASEB Journal. 22:3785-3794
Publication Year :
2008
Publisher :
Wiley, 2008.

Abstract

Axin is a scaffold protein for the β-catenin destruction complex, and a negative regulator of canonical Wnt signaling. Previous studies implicated the six C-terminal amino acids (C6 motif) in the ability of Axin to activate c-Jun N-terminal kinase, and identified them as a SUMOylation target. Deletion of the C6 motif of mouse Axin in vivo reduced the steady-state protein level, which caused embryonic lethality. Here, we report that this deletion (Axin-ΔC6) causes a reduced half-life in mouse embryonic fibroblasts and an increased susceptibility to ubiquitination in HEK 293T cells. We confirmed the C6 motif as a SUMOylation target in vitro, and found that mutating the C-terminal SUMOylation target residues increased the susceptibility of Axin to polyubiquitination and reduced its steady-state level. Heterologous SUMOylation target sites could replace C6 in providing this protective effect. These findings suggest that SUMOylation of the C6 motif may prevent polyubiquitination, thus increasing the stability of Axin. Although C6 deletion also caused increased association of Axin with Dvl-1, this interaction was not altered by mutating the lysine residues in C6, nor could heterologous SUMOylation motifs replace the C6 motif in this assay. Therefore, some other specific property of the C6 motif seems to reduce the interaction of Axin with Dvl-1.—Kim, M. J., Chia, I. V., Costantini, F. SUMOylation target sites at the C terminus protect Axin from ubiquitination and confer protein stability.

Details

ISSN :
15306860 and 08926638
Volume :
22
Database :
OpenAIRE
Journal :
The FASEB Journal
Accession number :
edsair.doi.dedup.....b2b88349ef98cd2f11b041cf21e9326d
Full Text :
https://doi.org/10.1096/fj.08-113910