APC Is Essential for Targeting Phosphorylated β-Catenin to the SCFβ-TrCP Ubiquitin Ligase
In: Molecular Cell, Jg. 32 (2008-12-01), S. 652-661
Online
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Zugriff:
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.
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APC Is Essential for Targeting Phosphorylated β-Catenin to the SCFβ-TrCP Ubiquitin Ligase
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Autor/in / Beteiligte Person: | Su, Yunyun ; Day, Billy W. ; Ishikawa, Shinji ; Stella, Alessandra ; Shitoh, Kazuhisa ; Fu, Chunjiang ; Liu, Bo ; Schreiber, Emanuel M. ; Kojima, Masayuki |
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Zeitschrift: | Molecular Cell, Jg. 32 (2008-12-01), S. 652-661 |
Veröffentlichung: | Elsevier BV, 2008 |
Medientyp: | unknown |
ISSN: | 1097-2765 (print) |
DOI: | 10.1016/j.molcel.2008.10.023 |
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