REPLACEMENT OF PROTEASOME SUBUNIT-X AND SUBUNIT-Y BY LMP7 AND LMP2 INDUCED BY INTERFERON-GAMMA FOR ACQUIREMENT OF THE FUNCTIONAL DIVERSITY RESPONSIBLE FOR ANTIGEN-PROCESSING

Proteasomes catalyze the non-lysosomal, ATP-dependent selective breakdown of ubiquitinated proteins and are thought to be responsible for MHC class I-restricted antigen presentation. Recently we reported that gamma interferon (IFN-gamma) induced not only marked synthesis of the MHC-encoded proteasome subunits LMP2 and LMP7, but also almost complete loss of two unidentified proteasome subunits tentatively designated as X and Y in various human cells. Here, we show that subunit X is a new proteasomal subunit highly homologous to LMP7, and that subunit Y is identical to the LMP2-related proteasomal subunit delta. Thus, IFN-gamma appears to induce subunit replacements of X and Y by LMP7 and LMP2 respectively, producing 'immuno-proteasomes' with the functional diversity responsible for processing of endogenous antigens.