title: O-GlcNAc modification is an endogenous inhibitor of the proteasome.
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.
authors.affiliation: Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Fengxue
authors.initials: F
authors.lastname: Zhang
authors.forename: Kaihong
authors.initials: K
authors.lastname: Su
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Yang
authors.forename: Damon B
authors.initials: DB
authors.lastname: Bowe
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Paterson
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Kudlow
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D016329:Sp1 Transcription Factor / Q000378:metabolism; D014452:Ubiquitins / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D009097:Multienzyme Complexes; D010455:Peptides; D011506:Proteins; D034741:RNA, Small Interfering; D016329:Sp1 Transcription Factor; D014452:Ubiquitins; D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D000251:Adenosine Triphosphatases