Abstract
The proteasome is a 700-kD multisubunit enzyme complex with several proteolytically active sites. The enzyme complex is involved in both ubiquitin-dependent and -independent protein degradation and may contribute to the processing of antigens presented by major histocompatibility complex (MHC) class I molecules. Here we demonstrate that treatment of mouse fibroblast cells with 20 U interferon qr (IFN-y) for 3 d induces a change in the proteasome subunit composition and that the B-type subunit LMP2, which is encoded in the MHC class II region, is incorporated into the enzyme complex. This is paralleled by reduction of the homologous 6-subunit. IFN-3' stimulation results in a downregulation of the chymotrypsin-like Suc-LLVY-MCA peptide hydrolyzing activity of 20S proteasomes whereas the trypsin-like activity remains unaffected. When tested as a substrate a synthetic 25-mer polypeptide whose sequence covers the antigenic nonapeptide YPHFMPTNL of the MCMV pp89, 20S proteasomes of IFN-3'-induced cells exhibit altered chymotrypsin-like cleavage site preferences. In the absence of IFN-qr induction, the naturally processed nonamer peptide that is presented by MHC class.I molecules appears as a minor cleavage product. IFN-'y activation does not result in an increase of the final peptide but results in a different set of peptides. We hypothesize that these peptides represent precursor peptides that can be trimmed to final peptide size.
Item Type: | Journal article |
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Faculties: | Medicine |
Subjects: | 600 Technology > 610 Medicine and health |
URN: | urn:nbn:de:bvb:19-epub-6599-5 |
Item ID: | 6599 |
Date Deposited: | 21. Oct 2008, 08:45 |
Last Modified: | 29. Apr 2016, 09:00 |