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Protein phosphatase 2A and its B56 regulatory subunit inhibit Wnt signaling in Xenopus.

Publication ,  Journal Article
Li, X; Yost, HJ; Virshup, DM; Seeling, JM
Published in: EMBO J
August 1, 2001

Wnt signaling increases beta-catenin abundance and transcription of Wnt-responsive genes. Our previous work suggested that the B56 regulatory subunit of protein phosphatase 2A (PP2A) inhibits Wnt signaling. Okadaic acid (a phosphatase inhibitor) increases, while B56 expression reduces, beta-catenin abundance; B56 also reduces transcription of Wnt-responsive genes. Okadaic acid is a tumor promoter, and the structural A subunit of PP2A is mutated in multiple cancers. Taken together, the evidence suggests that PP2A is a tumor suppressor. However, other studies suggest that PP2A activates Wnt signaling. We now show that the B56, A and catalytic C subunits of PP2A each have ventralizing activity in Xenopus embryos. B56 was epistatically positioned downstream of GSK3beta and axin but upstream of beta-catenin, and axin co-immunoprecipitated B56, A and C subunits, suggesting that PP2A:B56 is in the beta-catenin degradation complex. PP2A appears to be essential for beta-catenin degradation, since beta-catenin degradation was reconstituted in phosphatase-depleted Xenopus egg extracts by PP2A, but not PP1. These results support the hypothesis that PP2A:B56 directly inhibits Wnt signaling and plays a role in development and carcinogenesis.

Duke Scholars

Published In

EMBO J

DOI

ISSN

0261-4189

Publication Date

August 1, 2001

Volume

20

Issue

15

Start / End Page

4122 / 4131

Location

England

Related Subject Headings

  • beta Catenin
  • Zebrafish Proteins
  • Xenopus laevis
  • Xenopus Proteins
  • Wnt Proteins
  • Trans-Activators
  • Signal Transduction
  • Repressor Proteins
  • Rats
  • Proto-Oncogene Proteins
 

Citation

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Li, X., Yost, H. J., Virshup, D. M., & Seeling, J. M. (2001). Protein phosphatase 2A and its B56 regulatory subunit inhibit Wnt signaling in Xenopus. EMBO J, 20(15), 4122–4131. https://doi.org/10.1093/emboj/20.15.4122
Li, X., H. J. Yost, D. M. Virshup, and J. M. Seeling. “Protein phosphatase 2A and its B56 regulatory subunit inhibit Wnt signaling in Xenopus.EMBO J 20, no. 15 (August 1, 2001): 4122–31. https://doi.org/10.1093/emboj/20.15.4122.
Li X, Yost HJ, Virshup DM, Seeling JM. Protein phosphatase 2A and its B56 regulatory subunit inhibit Wnt signaling in Xenopus. EMBO J. 2001 Aug 1;20(15):4122–31.
Li, X., et al. “Protein phosphatase 2A and its B56 regulatory subunit inhibit Wnt signaling in Xenopus.EMBO J, vol. 20, no. 15, Aug. 2001, pp. 4122–31. Pubmed, doi:10.1093/emboj/20.15.4122.
Li X, Yost HJ, Virshup DM, Seeling JM. Protein phosphatase 2A and its B56 regulatory subunit inhibit Wnt signaling in Xenopus. EMBO J. 2001 Aug 1;20(15):4122–4131.

Published In

EMBO J

DOI

ISSN

0261-4189

Publication Date

August 1, 2001

Volume

20

Issue

15

Start / End Page

4122 / 4131

Location

England

Related Subject Headings

  • beta Catenin
  • Zebrafish Proteins
  • Xenopus laevis
  • Xenopus Proteins
  • Wnt Proteins
  • Trans-Activators
  • Signal Transduction
  • Repressor Proteins
  • Rats
  • Proto-Oncogene Proteins