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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
- 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.
- Subjects :
- Scaffold protein
Beta-catenin
Amino Acid Motifs
Dishevelled Proteins
SUMO protein
Heterologous
macromolecular substances
Biology
Biochemistry
Cell Line
Research Communications
Mice
Axin Protein
Ubiquitin
Genetics
Animals
Humans
Amino Acid Sequence
Molecular Biology
Adaptor Proteins, Signal Transducing
Sequence Deletion
Kinase
C-terminus
Ubiquitination
Wnt signaling pathway
Phosphoproteins
Molecular biology
Repressor Proteins
Wnt Proteins
biology.protein
Signal Transduction
Biotechnology
Subjects
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