APC Is Essential for Targeting Phosphorylated beta-Catenin to the SCF(beta-TrCP) Ubiquitin Ligase

作者：Su YunYun; Fu Chunjiang; Ishikawa Shinji; Stella Alessandra; Kojima Masayuki; Shitoh Kazuhisa; Schreiber Emanuel M; Day Billy W; Liu Bo^*

来源：Molecular Cell, 2008, 32(5): 652-661.

DOI：10.1016/j.molcel.2008.10.023

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.

• 出版日期2008-12-5