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

AUTOR(ES)

Li, Xinghai

FONTE

Oxford University Press

RESUMO

Wnt signaling increases β-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, β-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 GSK3β and axin but upstream of β-catenin, and axin co-immunoprecipitated B56, A and C subunits, suggesting that PP2A:B56 is in the β-catenin degradation complex. PP2A appears to be essential for β-catenin degradation, since β-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.

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