phosphorylation site mutants of CTNNB1 are not targeted to the proteasome by the destruction complex

Stable Identifier
R-HSA-4839743
Type
Pathway
Species
Homo sapiens
Compartment
cytosol
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phosphorylation site mutants of CTNNB1 are not targeted to the proteasome by the destruction complex
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Mutations in exon 3 of the beta-catenin gene have been identified in a number of human cancers (Morin et al, 1997; Rubinfeld et al, 1997; reviewed in Polakis, 2000; Polakis, 2007). These mutations generally affect serine and threonine residues (S33, S37, T41, S45) that are the sites of phosphorylation by CK1 and GSK3; phosphorylation of these residues is required for the ubiquitin-mediated degradation of beta-catenin. Hence mutation of these phospho-acceptor sites stabilizes beta-catenin, allowing it to accumulate, translocate to the nucleus and activate WNT signaling through association with LEF1/TCF DNA binding partners (Hart et al, 1999; Peifer and Polakis, 2000; Laurent-Puig et al, 2001; reviewed in Saito-Diaz et al, 2013).

Literature References
PubMed ID Title Journal Year
11375957 Genetic alterations associated with hepatocellular carcinomas define distinct pathways of hepatocarcinogenesis

Laurent-Puig, P, Legoix, P, Bluteau, O, Belghiti, J, Franco, D, Binot, F, Monges, G, Thomas, G, Bioulac-Sage, P, Zucman-Rossi, J

Gastroenterology 2001
9065403 Stabilization of beta-catenin by genetic defects in melanoma cell lines

Rubinfeld, B, Robbins, P, El-Gamil, M, Albert, I, Porfiri, E, Polakis, P

Science 1997
9065402 Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC

Morin, PJ, Sparks, AB, Korinek, V, Barker, N, Clevers, HC, Vogelstein, B, Kinzler, KW

Science 1997
10733430 Wnt signaling in oncogenesis and embryogenesis--a look outside the nucleus

Peifer, M, Polakis, P

Science 2000
23256519 The way Wnt works: Components and mechanism

Saito-Diaz, K, Chen, TW, Wang, X, Thorne, CA, Wallace, HA, Page-McCaw, A, Lee, E

Growth Factors 2013
9601641 Downregulation of beta-catenin by human Axin and its association with the APC tumor suppressor, beta-catenin and GSK3 beta

Hart, MJ, de los Santos, R, Albert, IN, Rubinfeld, B, Polakis, P

Curr. Biol. 1998
Participants
Events
Participant Of
hasEvent
Disease
Name Identifier Synonyms
cancer 162 malignant tumor, malignant neoplasm, primary cancer
Authored
Rothfels, K  (2013-11-01)
Reviewed
Salahshor, S  (2014-05-12)
Woodgett, J  (2014-05-21)
Created
Rothfels, K  (2013-11-02)