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Science 26 March 1999:
Vol. 283. no. 5410, pp. 2089 - 2091
DOI: 10.1126/science.283.5410.2089
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Reports

Regulation of beta -Catenin Signaling by the B56 Subunit of Protein Phosphatase 2A

Joni M. Seeling, 1 Jeffrey R. Miller, 3 Rosario Gil, 1* Randall T. Moon, 3 Ray White, 1 David M. Virshup 12dagger

Dysregulation of Wnt-beta -catenin signaling disrupts axis formation in vertebrate embryos and underlies multiple human malignancies. The adenomatous polyposis coli (APC) protein, axin, and glycogen synthase kinase 3beta form a Wnt-regulated signaling complex that mediates the phosphorylation-dependent degradation of beta -catenin. A protein phosphatase 2A (PP2A) regulatory subunit, B56, interacted with APC in the yeast two-hybrid system. Expression of B56 reduced the abundance of beta -catenin and inhibited transcription of beta -catenin target genes in mammalian cells and Xenopus embryo explants. The B56-dependent decrease in beta -catenin was blocked by oncogenic mutations in beta -catenin or APC, and by proteasome inhibitors. B56 may direct PP2A to dephosphorylate specific components of the APC-dependent signaling complex and thereby inhibit Wnt signaling.

1 Department of Oncological Sciences, Huntsman Cancer Institute, and
2 Department of Pediatrics, University of Utah, Salt Lake City, UT 84132, USA.
3 Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
*   Present address: Departamento de Bioquimica y Biologia Molecular, Universitat de Valencia, Apartado de Correos 73, 46100 Burjassot (Valencia), Spain.

dagger    To whom correspondence should be addressed. E-mail: david.virshup{at}hci.utah.edu

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D. H. Song, D. J. Sussman, and D. C. Seldin (2000)
J. Biol. Chem. 275, 23790-23797
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Casein kinase I phosphorylates and destabilizes the beta -catenin degradation complex.
Z.-H. Gao, J. M. Seeling, V. Hill, A. Yochum, and D. M. Virshup (2002)
PNAS 99, 1182-1187
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Phosphorylation near nuclear localization signal regulates nuclear import of adenomatous polyposis coli protein.
F. Zhang, R. L. White, and K. L. Neufeld (2000)
PNAS 97, 12577-12582
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