APC is essential for targeting phosphorylated beta-catenin to the SCFbeta-TrCP ubiquitin ligase.

Abstract:

:Ubiquitin-dependent proteolysis is an important mechanism that suppresses the beta-catenin transcription factor in cells without Wnt stimulation. A critical step in this regulatory pathway is to create a SCF(beta-TrCP) E3 ubiquitin ligase binding site for beta-catenin. Here we show that the SCF(beta-TrCP) binding site created by phosphorylation of beta-catenin is highly vulnerable to protein phosphatase 2A (PP2A) and must be protected by the adenomatous polyposis coli (APC) tumor suppressor protein. Specifically, phosphorylated beta-catenin associated with the wild-type APC protein is recruited to the SCF(beta-TrCP) complex, ubiquitin conjugated, and degraded. A mutation in APC that deprives this protective function exposes the N-terminal phosphorylated serine/threonine residues of beta-catenin to PP2A. Dephosphorylation at these residues by PP2A eliminates the SCF(beta-TrCP) recognition site and blocks beta-catenin ubiquitin conjugation. Thus, by acting to protect the E3 ligase binding site, APC ensures the ubiquitin conjugation of phosphorylated beta-catenin.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Su Y,Fu C,Ishikawa S,Stella A,Kojima M,Shitoh K,Schreiber EM,Day BW,Liu B

doi

10.1016/j.molcel.2008.10.023

subject

Has Abstract

pub_date

2008-12-05 00:00:00

pages

652-61

issue

5

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(08)00764-8

journal_volume

32

pub_type

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