Newly identified pair of proteasomal subunits regulated reciprocally by interferon γ

Abstract

Interferon (IFN) γ induces replacements of the proteasomal subunits X and Y by LMP7 and LMP2, respectively, resulting in an alteration of the proteolytic specificity. We found a third pair of proteasome subunits expressed reciprocally in response to IFN-γ. Molecular cloning of a cDNA encoding one subunit designated as Z, downregulated by IFN-γ, showed that it is a novel proteasomal submit with high homology to MECL1, which is markedly induced by IFN-γ. Thus, IFN-γ induces submit replacements of not only X and Y by LMP7 and LMP2, respectively, but also of Z by MECL1, producing proteasomes responsible for immunological processing of endogenous antigens. When processed from their precursors, three pairs of the 10 homologous, but distinct, β-type subunits of eukaryotic proteasomes, that is, X/LMP7, Y/LMP2, and Z/MECL1, have an NH2-terminal threonine residue, assumed to be part of a catalytic center. These findings suggest that the altered molecular organization of the proteasome induced by IFN-γ may be responsible for acquisition of its functional change.