O-GlcNAc Modification Is an Endogenous Inhibitor of the Proteasome

• Published in: Cell Vol. 115; no. 6; pp. 715 - 725
• Main Authors: Zhang, Fengxue, Su, Kaihong, Yang, Xiaoyong, Bowe, Damon B., Paterson, Andrew J., Kudlow, Jeffrey E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12.12.2003
• Subjects: Adenosine Triphosphatases - metabolism; Amino Acids - metabolism; Animals; Cell Line; Cysteine Endopeptidases - metabolism; Energy Metabolism - physiology; Multienzyme Complexes - antagonists & inhibitors; Multienzyme Complexes - metabolism; N-Acetylglucosaminyltransferases - metabolism; OGT protein; Peptides - metabolism; Proteasome Endopeptidase Complex; Proteins - metabolism; Rats; RNA, Small Interfering - pharmacology; Sp1 Transcription Factor - metabolism; Ubiquitins - metabolism
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(03)00974-7

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.