Endoplasmic reticulum aminopeptidases

Fruci, D., Ferracuti, S., Limongi, M. Z., Consolo, V., Giorda, E., Fra ioli, R., Sibilio, L., Carroll, 0., Hattori, A., van Endert P. M., and Giacomini, P., 2006, Expression of endoplasmic reticulum aminopeptidases in EBV B cell lines from healthy donors and in leucemia/lymphoma, carcinoma, and melanoma cell lines, J. of Immunol. 176 4869-4879. 

Proteasomes rather than cytosolic carboxy-peptidases act to trim the C-terminal amino acids to conform the peptide to the proper size for MHC class-I presentation. Presentation from N-extended precursors is inhibited by acetylation of the terminal a-amino group at the N-terminus [354], which prevents the peptide to be cleaved by aminopeptidases e.g. leucine aminopeptidase) but not by proteasomes or endopeptidases. The TAP system transports peptides to the ER including both mature epitopes and longer precursors. It seems then that the peptides to be presented by MHC class-I can arise from N-extended precursors both in the cytosol and in the endoplasmic reticulum (ER). This assertion has been experimentally confirmed [355,356]. 

Proteasomes are the major cytosolic and nuclear protein degradation machineries and they are also responsible for the proteolysis of misfolded, ER-dislocated (endoplasmic reticulum) proteins [1-3]. Proteasomal protein turnover takes place in an ubiquitin-dependent manner. The proteasome-generated products - ohgopeptides varying in length from 3 to up to 30 amino acid residues - are further processed by aminopeptidases. In higher vertebrates, antigenic peptides are selected from the peptide pool produced by proteasomes and downstream aminopeptidases for presentation on the outer cell surface by major histocompatibility class 1 (MHCl) protein complexes. In this way, proteasomes are essential factors in the detection and eradication of virally infected cells. 

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