O-GlcNAc modification is an endogenous inhibitor of the proteasome

Academic Article

Abstract

  • The ubiquitin proteasome system classically selects its substrates for degradation by tagging them with ubiquitin. Here, we describe another means of controlling proteasome function in a global manner. The 26S proteasome can be inhibited by modification with the enzyme, O-GlcNAc transferase (OGT). This reversible modification of the proteasome inhibits the proteolysis of the transcription factor Sp1 and a hydrophobic peptide through inhibition of the ATPase activity of 26S proteasomes. The Rpt2 ATPase in the mammalian proteasome 19S cap is modified by O-GlcNAc in vitro and in vivo and as its modification increases, proteasome function decreases. This mechanism may couple proteasomes to the general metabolic state of the cell. The O-GlcNAc modification of proteasomes may allow the organism to respond to its metabolic needs by controlling the availability of amino acids and regulatory proteins.
  • Digital Object Identifier (doi)

    Author List

  • Zhang F; Su K; Yang X; Bowe DB; Paterson AJ; Kudlow JE
  • Start Page

  • 715
  • End Page

  • 725
  • Volume

  • 115
  • Issue

  • 6