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 Celljournal_title
Molecular cellauthors
Su Y,Fu C,Ishikawa S,Stella A,Kojima M,Shitoh K,Schreiber EM,Day BW,Liu Bdoi
10.1016/j.molcel.2008.10.023subject
Has Abstractpub_date
2008-12-05 00:00:00pages
652-61issue
5eissn
1097-2765issn
1097-4164pii
S1097-2765(08)00764-8journal_volume
32pub_type
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