Misspliced GSK3beta mutants stabilize beta-catenin levels

Stable Identifier
Reaction [transition]
Homo sapiens
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GSK3beta mRNA is subject to aberrant splicing in stem cells in chronic myeloid leukemia. Missplicing leads to in-frame deletion of exons 8 and 9 which encode the FRAT and AXIN binding domains of the protein (Jamieson et al, 2008; Abrahamsson et al, 2009). Cells expressing the mutant GSK3beta have elevated levels of nuclear beta-catenin and high levels of TCF-dependent reporter activity (Jamieson et al, 2008; Abrahamsson et al, 2009). Although it is possible that the defect in the ability of mutant GSK3beta to promote beta-catenin degradation arises from an inability to bind to AXIN and form a functional degradation complex, this has not been formally demonstrated.

Literature References
PubMed ID Title Journal Year
15306667 Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML

Weissman, IL, Jones, C, Jamieson, CH, Manz, MG, Gotlib, J, Ailles, LE, Muijtjens, M, Zehnder, JL, Keating, A, Li, K, Dylla, SJ, Sawyers, CL

N. Engl. J. Med. 2004
19237556 Glycogen synthase kinase 3beta missplicing contributes to leukemia stem cell generation

Weissman, IL, Creusot, RS, Newton, IG, Barroga, CF, Abrahamsson, AE, Negrin, RS, Keating, A, Karimi, M, Jones, C, Jamieson, CH, Giles, FJ, Gotlib, J, Zehnder, JL, Geron, I, Durocher, J, Dao, KH

Proc. Natl. Acad. Sci. U.S.A. 2009
Normal reaction
Functional status

Loss of function of pS45-beta-catenin:p-Axin:GSK3 del304-316:CK1alpha:APC:PP2A:AMER1 complex [cytosol]

Name Identifier Synonyms
chronic myeloid leukemia DOID:8552 CML, chronic myelogenous leukemia, no ICD-O subtype (morphologic abnormality), chronic myeloid leukemia, disease (disorder), chronic myeloid leukemia without mention of remission, CML - chronic Myelogenous Leukemia, chronic myeloid leukemia in remission (disorder), Myeloid Leukemia, chronic, CML in Remission, chronic myeloid leukemia in remission, chronic myeloid leukaemia, chronic myeloid leukemia NOS (disorder)
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