act(complex(GO:"proteasome complex")) negativeCorrelation a(HBP:"O-GlcNAcylation")

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PubMed:19732809

It has been reported that the proteasomal machinery is modified by O-GlcNAcylation [53,126] and that after modification by OGT, the proteasome is inhibited [53]. Intriguingly, it has been proposed that a genetic impairment in the OGA gene results in proteasomal dysfunction through a lack of hydrolysis of the inhibitory O-GlcNAc residues of the 19S regulatory cap. Indeed, the OGA gene is located in the 10q locus [127,128], a chromosomal region frequently mutated in AD. The impairment of OGA in AD and the subsequent static OGlcNAcylation of the proteasome may explain why the latter fails to degrade neuronal aggregates. In addition, it has been reported that OGlcNAcylation reduces the sensitivity of intracellular proteins to proteasomal degradation by directly modifying them [43,129,130]. The two phenomena could thus act synergistically: a protein could escape degradation by means of its own O-GlcNAcylation and by the inhibitory effect of glycosylation on the proteasome, leading to a considerable decrease in the turnover of proteins that in turn may aggregate and cause neuronal death.

Related Edges 3

• a(HBP:"O-GlcNAcylation") negativeCorrelation act(complex(GO:"proteasome complex"))
• act(complex(GO:"proteasome complex")) positiveCorrelation g(HGNC:OGT)
• g(HGNC:OGT) positiveCorrelation act(complex(GO:"proteasome complex"))

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