Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.24.56 (
insulin-degrading enzyme
)
737
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Antigen presentation by MHC class I molecules requires degradation of epitope source proteins in the cytosol. Although the preeminent role of the proteasome is clearly established, evidence suggesting a significant role for proteasome-independent generation of class I ligands has been reported repeatedly. However, an enzyme responsible for such a role has not been identified. Recently
insulin-degrading enzyme
(
IDE
) was shown to produce an antigenic peptide derived from the tumor antigen MAGE-A3 in an entirely proteasome-independent manner, raising the question of the global impact of
IDE
in
MHC class I antigen
processing. Here we report that
IDE
knockdown in human cell lines, or knockout in two different mouse strains, has no effect on cell surface expression of various MHC class I molecules, including allomorphs such as HLA-A3 and HLA-B27 suggested to be loaded in an at least a partly proteasome-independent manner. Moreover, reduced or absent
IDE
expression does not affect presentation of five epitopes including epitopes derived from beta amyloid and proinsulin, two preferred
IDE
substrates. Thus,
IDE
does not play a major role in
MHC class I antigen
processing, confirming the dominant and almost exclusive role of the proteasome in cytosolic production of MHC class I ligands.
...
PMID:No major role for insulin-degrading enzyme in antigen presentation by MHC molecules. 2451 42
