The eukaryotic multi-catalytic proteinase complex, otherwise known as the proteasome, is present in both the nucleus and cytoplasm of cells and contains at least 15 nonidentical subunits, which form a highly ordered ring-shaped structure. The proteasome is involved in an ATP/Ubiquitin-dependent proteolytic pathway and expresses at least five distinct proteolytic activities, including the cleavage of peptides after branched-chain amino acids or bulky hydrophobic amino acids. Two components of the proteasome are the low molecular mass proteins LMP2 and LMP7, which are thought to connect the proteasome to the MHC class-I antigen-processing pathway. Upon stimulation with IFN-γ, LMP2 and LMP7 displace housekeeping subunits in the proteasome and activate cytotoxic T cells (CTLs). LMP2 and LMP7 are produced as precursor proteins, which are processed to subunits that have the ability to complex with the proteasome. LMP2 is expressed as two alternatively spliced forms, LMP2.l and LMP2.s, in lymphoblastoid cell lines and in fibroblasts after IFN-γ stimulation. LMP7 is also expressed as two forms, LMP7A and LMP7B, also designated LMP7-E1 and E2, in several tissues.
