Abstract:
:Most antigenic peptides presented by major histocompatibility complex (MHC) class I molecules are produced by the proteasome. Here we show that a proteasome-independent peptide derived from the human tumor protein MAGE-A3 is produced directly by insulin-degrading enzyme (IDE), a cytosolic metallopeptidase. Cytotoxic T lymphocyte recognition of tumor cells was reduced after metallopeptidase inhibition or IDE silencing. Separate inhibition of the metallopeptidase and the proteasome impaired degradation of MAGE-A3 proteins, and simultaneous inhibition of both further stabilized MAGE-A3 proteins. These results suggest that MAGE-A3 proteins are degraded along two parallel pathways that involve either the proteasome or IDE and produce different sets of antigenic peptides presented by MHC class I molecules.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Parmentier N,Stroobant V,Colau D,de Diesbach P,Morel S,Chapiro J,van Endert P,Van den Eynde BJdoi
10.1038/ni.1862subject
Has Abstractpub_date
2010-05-01 00:00:00pages
449-54issue
5eissn
1529-2908issn
1529-2916pii
ni.1862journal_volume
11pub_type
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