Signaling by CTNNB1 phospho-site mutants

Stable Identifier
R-HSA-4839743
Type
Pathway
Species
Homo sapiens
Compartment
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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
9065403 Stabilization of beta-catenin by genetic defects in melanoma cell lines

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

Science 1997
11375957 Genetic alterations associated with hepatocellular carcinomas define distinct pathways of hepatocarcinogenesis

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

Gastroenterology 2001
9065402 Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC

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

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

Polakis, P, Peifer, M

Science 2000
23256519 The way Wnt works: Components and mechanism

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

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

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

Curr. Biol. 1998
Participants
Participates
Disease
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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Reviewed
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