Desumoylation Activity of Axam, a Novel Axin-Binding Protein, Is Involved in Downregulation of β-Catenin
| Autor: | Toshimasa Asahara, Hideki Yamamoto, Makoto Asashima, Akimasa Fukui, Toshiaki Suzuki, Keiji Tanaka, Takayuki Kadoya, Akira Kikuchi, Tatsuo Michiue, Akira Yukita |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Beta-catenin
SENP1 Recombinant Fusion Proteins Xenopus Molecular Sequence Data SUMO-1 Protein SUMO protein Down-Regulation Xenopus Proteins Cell Line Axin Protein Downregulation and upregulation Proto-Oncogene Proteins Animals Humans Amino Acid Sequence Cell Growth and Development Molecular Biology beta Catenin Adaptor Proteins Signal Transducing Body Patterning Binding Sites Base Sequence Sequence Homology Amino Acid biology Wnt signaling pathway Proteins DNA Cell Biology Zebrafish Proteins biology.organism_classification Molecular biology Protein Structure Tertiary Rats Repressor Proteins Wnt Proteins Cytoskeletal Proteins Amino Acid Substitution Catenin Trans-Activators biology.protein Carrier Proteins Signal Transduction |
| Zdroj: | Molecular and Cellular Biology. 22:3803-3819 |
| ISSN: | 1098-5549 |
| DOI: | 10.1128/mcb.22.11.3803-3819.2002 |
| Popis: | Axam has been identified as a novel Axin-binding protein that inhibits the Wnt signaling pathway. We studied the molecular mechanism by which Axam stimulates the downregulation of beta-catenin. The C-terminal region of Axam has an amino acid sequence similar to that of the catalytic region of SENP1, a SUMO-specific protease (desumoylation enzyme). Indeed, Axam exhibited activity to remove SUMO from sumoylated proteins in vitro and in intact cells. The Axin-binding domain is located in the central region of Axam, which is different from the catalytic domain. Neither the Axin-binding domain nor the catalytic domain alone was sufficient for the downregulation of beta-catenin. An Axam fragment which contains both domains was able to decrease the level of beta-catenin. On substitution of Ser for Cys(547) in the catalytic domain, Axam lost its desumoylation activity. Further, this Axam mutant decreased the activity to downregulate beta-catenin. Although Axam strongly inhibited axis formation and expression of siamois, a Wnt-response gene, in Xenopus embryos, Axam(C547S) showed weak activities. These results demonstrate that Axam functions as a desumoylation enzyme to downregulate beta-catenin and suggest that sumoylation is involved in the regulation of the Wnt signaling pathway. |
| Databáze: | OpenAIRE |
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