Proteasome subunits X and Y alter peptidase activities in opposite ways to the interferon-γ-induced subunits LMP2 and LMP7

Maria Gaczynska, Alfred L. Goldberg, Keiji Tanaka, Klavs B. Hendil, Kenneth L. Rock

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123 Scopus citations

Abstract

Most antigenic peptides presented on major histocompatibility complex class I molecules are generated by proteasomes. Interferon-γ, which stimulates antigen presentation, induces new proteasome β-subunits LMP2 and LMP7, which replace the homologous β-subunits Y (δ) and X (ε). As a result, the capacity of the proteasome to cleave model peptides increases after hydrophobic and basic residues and falls after acidic residues. To clarify the function of these subunits, we examined the effects of overexpressing subunits X (δ) and Y (ε). Transfection of the Y gene into HeLa cells stimulated the proteasomal cleavage after acidic residues without altering other peptidase activities. This effect was proportional to the amount of the Y subunits and opposite to the effect of its homolog, LMP2. Y appears to promote cleavages after acidic residues. Furthermore, in mutants lacking the LMP genes (in contrast to wild-type cells), interferon-γ treatment increased the proteasome content of Y subunits and enhanced postacidic cleavages. Transfection with cDNA for the X subunit reduced hydrolysis after hydrophobic and basic residues, an effect opposite to transfection of LMP2 and LMP7. Surprisingly, transfection of X increased the amounts not only of X, but also of Y, while decreasing LMP2 content. Thus, the loss of the Y subunit upon interferon-γ treatment or LMP2 transfection accounts for the suppression of postacidic cleavages, and the loss of X contributes to the increased hydrolysis after hydrophobic and basic residues. These adaptations should favor the production of the kinds of peptides that are presented on major histocompatibility complex class I molecules.

Original languageEnglish (US)
Pages (from-to)17275-17280
Number of pages6
JournalJournal of Biological Chemistry
Volume271
Issue number29
DOIs
StatePublished - 1996

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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