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Oligopeptide Competition Assay for Phosphorylation Site Determination
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Oligopeptide Competition Assay for Phosphorylation Site Determination

Published on: May 18, 2017

Regulation of protein stability by GSK3 mediated phosphorylation

Chong Xu1, Nam-Gyun Kim, Barry M Gumbiner

  • 1Graduate Program of Molecular, Cellular and Developmental Biology, University of Virginia, Charlottesville, VA, USA.

Cell Cycle (Georgetown, Tex.)
|November 20, 2009
PubMed

Insights

Glycogen synthase kinase-3 (GSK3) regulates protein stability and cellular processes. This study identifies new GSK3 substrates, revealing phosphorylation-dependent proteolysis as a widespread cellular mechanism.

Area of Science:

  • Cellular Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Glycogen synthase kinase-3 (GSK3) is crucial in signaling pathways governing cell proliferation, differentiation, apoptosis, and embryonic development.
  • GSK3 mediates beta-catenin degradation in the Wnt signaling pathway through phosphorylation.
  • Recent findings indicate GSK3 and Wnt signaling regulate additional protein substrates, impacting cellular processes.

Purpose of the Study:

  • To identify novel protein substrates regulated by GSK3 and/or Wnt signaling.
  • To investigate proteins potentially controlled by GSK3 and beta-Trcp (an SCF E3 ubiquitin ligase).
  • To review literature on GSK3-regulated proteolysis substrates.

Main Methods:

  • Biochemical screening to discover protein substrates regulated by GSK3 and Wnt signaling.
  • Bio-informatics based screening for proteins targeted by GSK3 and beta-Trcp.
  • Literature review of GSK3-regulated proteolysis.

Main Results:

  • Identification of multiple new protein substrates whose stability is influenced by Wnt signaling and/or GSK3.
  • Bio-informatics screen suggests additional proteins may be regulated by GSK3 and beta-Trcp.
  • Literature review confirms various GSK3-regulated proteolysis substrates.

Conclusions:

  • GSK3 plays a significant role in regulating protein stability beyond beta-catenin.
  • Phosphorylation-dependent proteolysis by GSK3 is a widespread cellular mechanism.
  • This mechanism is employed by cells to control diverse cellular processes in response to signals.

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