O-GlcNAc modification is an endogenous inhibitor of the proteasome

Fengxue Zhang, Kaihong Su, Xiaoyong Yang, Damon B. Bowe, Andrew J. Paterson, Jeffrey E. Kudlow

Research output: Contribution to journalArticlepeer-review

323 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)715-725
Number of pages11
JournalCell
Volume115
Issue number6
DOIs
StatePublished - Dec 12 2003

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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