title: Aldolase positively regulates of the canonical Wnt signaling pathway.
abstract: The Wnt signaling pathway is an evolutionary conserved system, having pivotal roles during animal development. When over-activated, this signaling pathway is involved in cancer initiation and progression. The canonical Wnt pathway regulates the stability of β-catenin primarily by a destruction complex containing a number of different proteins, including Glycogen synthase kinase 3β (GSK-3β) and Axin, that promote proteasomal degradation of β-catenin. As this signaling cascade is modified by various proteins, novel screens aimed at identifying new Wnt signaling regulators were conducted in our laboratory. One of the different genes that were identified as Wnt signaling activators was Aldolase C (ALDOC). Here we report that ALDOC, Aldolase A (ALDOA) and Aldolase B (ALDOB) activate Wnt signaling in a GSK-3β-dependent mechanism, by disrupting the GSK-3β-Axin interaction and targeting Axin to the dishevelled (Dvl)-induced signalosomes that positively regulate the Wnt pathway thus placing the Aldolase proteins as novel Wnt signaling regulators.
authors.forename: Michal
authors.initials: M
authors.lastname: Caspi
authors.forename: Gili
authors.initials: G
authors.lastname: Perry
authors.forename: Nir
authors.initials: N
authors.lastname: Skalka
authors.forename: Shilhav
authors.initials: S
authors.lastname: Meisel
authors.forename: Anastasia
authors.initials: A
authors.lastname: Firsow
authors.forename: Maayan
authors.initials: M
authors.lastname: Amit
authors.affiliation: Department of Clinical Microbiology and Immunology, Sackler Faculty School of Medicine, Tel Aviv University, Ramat-Aviv, Tel Aviv 69978, Israel. arina@post.tau.ac.il.
authors.forename: Rina
authors.initials: R
authors.lastname: Rosin-Arbesfeld
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D060466:Axin Protein / Q000378:metabolism; D002460:Cell Line; D000072261:Dishevelled Proteins; D005634:Fructose-Bisphosphate Aldolase / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008954:Models, Biological; D050505:Mutant Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011817:Rabbits; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D060466:Axin Protein; D000072261:Dishevelled Proteins; D007527:Isoenzymes; D050505:Mutant Proteins; D010750:Phosphoproteins; D051176:beta Catenin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D005634:Fructose-Bisphosphate Aldolase