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 journalArticle

296 Citations (Scopus)

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

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Proteasome Inhibitors
Proteasome Endopeptidase Complex
Ubiquitin
Adenosine Triphosphatases
Sp1 Transcription Factor
Proteolysis
Availability
Amino Acids
Degradation
Peptides
Substrates
Enzymes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Zhang, F., Su, K., Yang, X., Bowe, D. B., Paterson, A. J., & Kudlow, J. E. (2003). O-GlcNAc modification is an endogenous inhibitor of the proteasome. Cell, 115(6), 715-725. https://doi.org/10.1016/S0092-8674(03)00974-7

O-GlcNAc modification is an endogenous inhibitor of the proteasome. / Zhang, Fengxue; Su, Kaihong; Yang, Xiaoyong; Bowe, Damon B.; Paterson, Andrew J.; Kudlow, Jeffrey E.

In: Cell, Vol. 115, No. 6, 12.12.2003, p. 715-725.

Research output: Contribution to journalArticle

Zhang, F, Su, K, Yang, X, Bowe, DB, Paterson, AJ & Kudlow, JE 2003, 'O-GlcNAc modification is an endogenous inhibitor of the proteasome', Cell, vol. 115, no. 6, pp. 715-725. https://doi.org/10.1016/S0092-8674(03)00974-7
Zhang F, Su K, Yang X, Bowe DB, Paterson AJ, Kudlow JE. O-GlcNAc modification is an endogenous inhibitor of the proteasome. Cell. 2003 Dec 12;115(6):715-725. https://doi.org/10.1016/S0092-8674(03)00974-7
Zhang, Fengxue ; Su, Kaihong ; Yang, Xiaoyong ; Bowe, Damon B. ; Paterson, Andrew J. ; Kudlow, Jeffrey E. / O-GlcNAc modification is an endogenous inhibitor of the proteasome. In: Cell. 2003 ; Vol. 115, No. 6. pp. 715-725.
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