Proposed Role of a γ-Interferon Inducible Proteasome-Regulator in Antigen Presentation
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 ß, according to their similarity to the α- and ß-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 ß 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.
KeywordsProteasome Subunit Soluble Protein Fraction Recombinant Regulator Plasmodium Knowlesi Peptide Hydrolysis
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- Chu-Ping, M., Slaughter, C. A., and DeMartino, G. N., 1992, Identification, purification, and characterization of a protein activator (PA28) of the 20S proteasome (macropain), J. Biol. Chem. 267:10515–10523.Google Scholar
- Fruh, K., Yang, Y, Arnold, D., Chambers, J., Wu, L., Waters, J. B., Spies, T., and Peterson, P. A., 1992, Displacement of housekeeping proteasome subunits by MHC-encoded LMPs: a newly discovered mechanism for modulating the multicatalytic proteinase complex, J. Biol. Chem. 267:22131–22140.PubMedGoogle Scholar
- Lathe, R., 1985, Synthetic oligonucleotide probes deduced from amino acid sequence data. Theoretical and practical considerations, Biochemistry 183:1–12.Google Scholar
- Milner, R. E., Baksh, S., Shemanko, C, Carpenter, M. R., Smilie, L., Vance, J. E., Opas, M., and Michalak, M., 1991, Calreticulin and not calsequestrin, is the major calcium binding protein of smooth muscle sarcoplasmic reticulum and liver endoplasmic reticulum, J. Biol. Chem. 266:7155–7165.PubMedGoogle Scholar
- Nikaido, T, Shimada, K., Shibata, M., Hata, M., Sakamoto, M., Takasaki, Y., Sato, C, Takahashi, T, and Nishida, Y, 1990, Cloning and nucleotide sequence of cDNA for Ki antigen, a highly conserved nuclear protein detected with sera from patients with systemic lupis erythematosus, Clin. Exp. Immunol. 79:209–214.PubMedCrossRefGoogle Scholar
- Peters, J. -M., Harris, J. R., and Kleinschmidt, J. A., 1991, Ultrastructure of the 26S complex containing the 20S cylinder particle (multicatalytic proteinase/proteasome), Eur. J. Biochem. 56:422–432.Google Scholar
- Realini, C. A., Rogers, S., and Rechsteiner, M., 1994 b, Proposed roles in protein-protein association and presentation of peptides by MHC class I receptors, FEBS Lett. 348:109–113.Google Scholar