O-GlcNAc modification is an endogenous inhibitor of the proteasome.
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.
Zhang
Fengxue
F
Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Su
Kaihong
K
Yang
Xiaoyong
X
Bowe
Damon B
DB
Paterson
Andrew J
AJ
Kudlow
Jeffrey E
JE
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*
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