Proposed role of a gamma-interferon inducible proteasome-regulator in antigen presentation.

Abstract

The 26S complex and the proteasome (also called 20S protease or multicatalytic protease, MCP) are major extralysosomal proteases involved in the regulation of cytosolic protein levels in eukaryotic cells (Tanaka et al., 1992 for review see Rechsteiner et al., 1993; Peters, 1994). The proteasome (Fig. 1 A) is a very abundant cellular component representing up to 1% of the cytoplasmic protein. It has been found in all eukaryotes and also in the archaebacterium Thermoplasma acidophilum (Zwickl et al., 1991). Although proteasomes have not been reported in prokaryotes, structural studies and sequencing data suggest a possible evolutionary relationship between the prokaryotic Clp and Lon proteases (for review see Maurizi, 1992), and the eukaryotic 26S and proteasomes (Rechsteiner et al., 1993; Arribas and Castano, 1993). The proteasome complex (Fig. 1 A) exists as a high molecular mass multimer (700 kDa) composed of at least 28 noncovalently associated subunits (20-32 kDa). The subunits share considerable inter-subunit homology, and have been classified into two subgroups, α and s, according to their similarity to the α- and s-subunit of the archaebacterial proteasome (Zwickl et al., 1991). The subunits are arranged in four stacked heptameric rings to form a hollow cylinder of 11 x 16 nm (Peters et al., 1991). Electron microscopy studies place a subunits at each end of the cylinder whereas s subunits, possibly containing the catalytic sites, form the two central rings. Proteasomes exhibit at least three separate catalytic activities, termed trypsin-like, chymotrypsin-like, and glutamic-site-like (Pereira et al., 1992; Rivett, 1993). The regulation of these proteolytic sites as well as the exact subunit composition of the complexes are still unclear.