O-GlcNAc peptide epoxyketones are recognized by mammalian proteasomes.
Cytosolic and nuclear proteins may be subject to both O-GlcNAcylation and proteasomal degradation. By means of activity-based profiling, we demonstrate that O-GlcNAc serine-containing peptide epoxyketones bind to the proteasome catalytic active sites and thus provide the first clear evidence that proteasomes recognize peptides post-translationally modified with a GlcNAc moiety.
Witte
Martin D
MD
Leiden Institute of Chemistry, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
Florea
Bogdan I
BI
Verdoes
Martijn
M
Adeyanju
Oloruntosin
O
Van der Marel
Gijs A
GA
Overkleeft
Herman S
HS
D000117:Acetylglucosamine / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D006801:Humans; D007659:Ketones / Q000378:metabolism*; D011480:Protease Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors; D011485:Protein Binding; D013194:Staining and Labeling
D007659:Ketones; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D046988:Proteasome Endopeptidase Complex; D000117:Acetylglucosamine