NEWLY IDENTIFIED PAIR OF PROSTEASOMAL SUBUNITS REGULATED RECIPROCALLYBY INTERFERON-GAMMA

Interferon (IFN) gamma induces replacements of the proteasomal subunit s X and Y by LMP7 and LMP2, respectively, resulting in an alteration o f the proteolytic specificity. We found a third pair of proteasome sub units expressed reciprocally in response to IFN-gamma. Molecular cloni ng of a cDNA encoding one subunit designated as Z, downregulated by IF N-gamma, showed that it is a novel proteasomal subunit with high homol ogy to MECL1, which is markedly induced by IFN-gamma. Thus, IFN-gamma induces subunit replacements of not only X and Y by LMP7 and LMP2, res pectively, but also of Z by MECL1, producing proteasomes responsible f or immunological processing of endogenous antigens. When processed fro m their precursors, three pairs of the 10 homologous, but distinct, be ta-type subunits of eukaryotic proteasomes, that is, X/LMP7, Y/LMP2, a nd Z/MECL1, have an NH2-terminal threonine residue, assumed to be part of a catalytic center. These findings sus est that the altered molecu lar organization of the proteasome induced by IFN-gamma may be respons ible for acquisition of its functional change.