Interferon y Stimulation Modulates the Proteolytic Activity and Cleavage Site Preference of 20S Mouse Proteasomes

Episode von Medizin - Open Access LMU - Teil 11/22 von Ludwig-Maximilians-Universität München · 1. Januar 1994

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.

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