title: Regulation of protein stability by GSK3 mediated phosphorylation.
abstract: Glycogen synthase kinase-3 (GSK3) plays important roles in numerous signaling pathways that regulate a variety of cellular processes including cell proliferation, differentiation, apoptosis and embryonic development. In the canonical Wnt signaling pathway, GSK3 phosphorylation mediates proteasomal targeting and degradation of beta-catenin via the destruction complex. We recently reported a biochemical screen that discovered multiple additional protein substrates whose stability is regulated by Wnt signaling and/or GSK3 and these have important implications for Wnt/GSK3 regulation of different cellular processes.(1) In this article, we also present a bio-informatics based screen for proteins whose stability may be controlled by GSK3 and beta-Trcp, the SCF E3 ubiquitin ligase that is responsible for beta-catenin degradation in the Wnt signaling pathway. Furthermore, we review various GSK3 regulated proteolysis substrates described in the literature. We propose that GSK3 phosphorylation dependent proteolysis is a widespread mechanism that the cell employs to regulate a variety of cell processes in response to signals.
authors.affiliation: Graduate Program of Molecular, Cellular and Developmental Biology, University of Virginia, Charlottesville, VA, USA.
authors.forename: Chong
authors.initials: C
authors.lastname: Xu
authors.forename: Nam-Gyun
authors.initials: NG
authors.lastname: Kim
authors.forename: Barry M
authors.initials: BM
authors.lastname: Gumbiner
mesh_terms: D000818:Animals; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D006801:Humans; D010447:Peptide Hydrolases / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D055550:Protein Stability; D015398:Signal Transduction / Q000502:physiology*; D054875:Ubiquitination / Q000502:physiology; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D051153:Wnt Proteins; D038362:Glycogen Synthase Kinase 3; D010447:Peptide Hydrolases