Axin Directly Interacts with Plakoglobin and Regulates Its Stability*
- From the Departments of ‡Biochemistry and§Second Surgery, Hiroshima University School of Medicine, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8551, Japan
Abstract
Plakoglobin is homologous to β-catenin. Axin, a Wnt signal negative regulator, enhances glycogen synthase kinase (GSK)-3β-dependent phosphorylation of β-catenin and stimulates the degradation of β-catenin. Therefore, we examined the effect of Axin on plakoglobin stability. Axin formed a complex with plakoglobin in COS cells and SW480 cells. Axin directly bound to plakoglobin, and this binding was inhibited by β-catenin. Axin promoted GSK-3β-dependent phosphorylation of plakoglobin. Furthermore, overexpression of Axin down-regulated the level of plakoglobin in SW480 cells. These results suggest that Axin regulates the stability of plakoglobin by enhancing its phosphorylation by GSK-3β and that Axin may act on β-catenin and plakoglobin in similar manners.
Footnotes
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↵* This work was supported by grants-in-aid for scientific research and for exploratory research from the Ministry of Education, Science, and Culture, Japan and by grants from the Yamanouchi Foundation for Research on Metabolic Disorders and the Uehara Memorial Foundation.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵¶ To whom correspondence should be addressed. Tel.: 81-82-257-5130; Fax: 81-82-257-5134; E-mail: akikuchi@mcai.med.hiroshima-u. ac.jp.
- Abbreviations:
- GSK-3β
-
glycogen synthase kinase-3β
- Tcf
-
T-cell-specific factor
- Lef
-
lymphoid enhancer binding factor
- APC
-
adenomatous polyposis coli
- HA
-
hemagglutinin
- MBP
-
maltose-binding protein
- GST
-
glutathioneS-transferase
- PBS
-
phosphate-buffered saline
- EGFP
-
enhanced green fluorescent protein
- rAxin
-
rat Axin
-
- Received June 21, 1999.
- The American Society for Biochemistry and Molecular Biology, Inc.
