title: Wnt Signaling Translocates Lys48-Linked  Polyubiquitinated Proteins to the Lysosomal  Pathway.
abstract: Cellular proteins are degraded in either proteasomes or lysosomes depending on the types of ubiquitin chains that covalently modify them. It is not known whether the choice between these two pathways is physiologically regulated. The Lys48-polyubiquitin chain is the major signal directing proteins for degradation in proteasomes. Here, we report the unexpected finding that canonical Wnt signaling translocates some K48-linked polyubiquitinated proteins to the endolysosomal pathway. Proteasomal target proteins, such as b-catenin, Smad1, and Smad4, were targeted into endolysosomes in a process dependent on GSK3 activity. Relocalization was also dependent on Axin1 and the multivesicular body (MVB) proteins HRS/Vps27 and Vps4. The Wnt-induced accumulation of K48-linked polyubiquitinated proteins in endolysosomal organelles was accompanied by a transient decrease in cellular levels of free mono-ubiquitin, which may contribute to Wnt-regulated stabilization of proteins (Wnt/ STOP). We conclude that Wnt redirects Lys48-polyubiquitinated proteins that are normally degraded in proteasomes to endolysosomes.
authors.forename: Hyunjoon
authors.initials: H
authors.lastname: Kim
authors.forename: Philipp
authors.initials: P
authors.lastname: Vick
authors.forename: Joshua
authors.initials: J
authors.lastname: Hedtke
authors.forename: Diego
authors.initials: D
authors.lastname: Ploper
authors.forename: Edward M
authors.initials: EM
authors.lastname: De Robertis
mesh_terms: D006801:Humans; D025821:Polyubiquitin / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D014178:Translocation, Genetic; D054875:Ubiquitination; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway
chemical_list: D011506:Proteins; D051153:Wnt Proteins; C018589:lysosomal proteins; D025821:Polyubiquitin