Canonical activation of the WNT/Beta-catenin pathway

Canonical activation of the WNT/β-catenin pathway. (a) In the absence of WNT/β-catenin cascade activation, there is an intracytoplasmic pool of β-catenin that is phosphorylated by a protein complex, known as the “destruction complex” (formed from the GSK-3β, Axin, APC, and CKI1α proteins) that will ubiquitinate the β-catenin, undergoing proteasomal degradation. As a result, β-catenin does not interact with the transcription factors. (b) When the Frizzled receptor binds any member of the WNT ligand family (WNT 1, 2, 3, 8a, 8b, 10a, 10b), it activates the pathway and β-catenin is translocated to the nucleus, where it interacts with the transcription factors (TCF/LEF, Pygo, Bcl-9, Gro/TLE) that in turn trans-activate (arrow) genes known to be associated with cell development, proliferation, and WNT regulation. LRP—low-density lipoprotein receptor-related protein; WNT—Wingless/Integrated; CKIα—casein kinase Iα; GSK-3β—glycogen synthase kinase-3 beta; APC—adenomatous polyposis coli; TCF/LEF—T-cell factor/lymphoid enhancer factor; Pygo—Pygopus protein; Bcl-9—B-cell lymphoma 9 protein; Gro/TLE—Drosophila Groucho/transducin-like enhancers of split; GLUL—glutamate-ammonia ligase; TBX3—T-box transcription factor 3; OAT—ornithine aminotransferase; HIF-1α—hypoxia inducible factor 1 subunit alpha; FOXO—forkhead box protein O1; SOX—SRY-related HMG-box genes; AXIN 2 gene; SP5—Sp5 transcription factor

Publication

Molecular Mechanisms in Tumorigenesis of Hepatocellular Carcinoma and in Target Treatments—An Overview (2024) Raluca-Margit Szilveszter, et al. Biomolecules. 2024 Jun;14(6). Figure: F2. Homo sapiens

Disease mentions