APC is K63-polyubiquitinated

Stable Identifier
R-HSA-5246693
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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In unstimulated cells, APC is K63 polyubiquitinated in a manner that depends on its association with AXIN. Although the precise timing of APC polyubiquitination is unclear, it is disrupted by abrogation of GSK3 kinase activity and in the presence of phosphodegron mutants of beta-catenin, suggesting that the formation of a functional destruction complex is required. Destruction complex formation is also dependent upon AXIN levels, which may be regulated at least in part by the balance of its ubiquitination and sumoylation (Kim et al, 2008).
Upon WNT3A stimulation, APC K63 polyubiquitination is lost coincident with disruption of the APC-AXIN interaction (Tran and Polakis, 2012). Interestingly, another study has shown that DVL is K63 polyubiquitinated upon WNT signaling (Tauriello et al, 2010), suggesting a possible model in which WNT signaling promotes a change in AXIN-K63 polyubiquitin binding partner to destabilize the destruction complex and promote pathway activation. Alternately, APC K63 polyubiquitination may protect beta-catenin from PP2A-mediated dephosphorylation and thus favour its degradation (Su et al, 2008).

Literature References
PubMed ID Title Journal Year
20227366 Loss of the tumor suppressor CYLD enhances Wnt/beta-catenin signaling through K63-linked ubiquitination of Dvl

Tauriello, DV, Haegebarth, A, Kuper, I, Edelmann, MJ, Henraat, M, Canninga-van Dijk, MR, Kessler, BM, Clevers, HC, Maurice, MM

Mol. Cell 2010
22761442 Reversible modification of adenomatous polyposis coli (APC) with K63-linked polyubiquitin regulates the assembly and activity of the ?-catenin destruction complex

Tran, H, Polakis, P

J. Biol. Chem. 2012
18632848 SUMOylation target sites at the C terminus protect Axin from ubiquitination and confer protein stability

Kim, MJ, Chia, IV, Costantini, F

FASEB J. 2008
19061640 APC is essential for targeting phosphorylated beta-catenin to the SCFbeta-TrCP ubiquitin ligase

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

Mol. Cell 2008
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
ubiquitin protein ligase activity of unknown ubiquitin ligase [cytosol]
Physical Entity
Activity
Authored
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Created