We recently described the production of spliced antigenic peptides by the proteasome, and we provided experimental evidence for a mechanism of transpeptidation that involves an acyl-enzme intermediate and is tightly linked to the proteolysis reaction (1, 2). This model implies that the choice of peptide fragments to be spliced is dictated only by the location of the prominent cleavage sites within the parental protein. We will provide additional evidence supporting this model, and describe the role of the proteasome in the production of a third spliced peptide, which was described previously by Hanada et al (3). We also observed that the standard proteasome and the immunoproteasome differ in their capacity to produce the three spliced peptides we have described. As they also differ in their preferential cleavage activity, this observation further supports the transpeptidation model. We have also obtained experimental evidence for the existence of novel proteasome types that are intermediate between the standard proteasome and the immunoproteasome, harboring only one or two of the three catalytic immunosubunits. The characterization of these intermediate proteasomes will be described, as well as their quantification in various cell lines and their function in the processing of antigenic peptides. 1. Vigneron, N., V. Stroobant, J. Chapiro, A. Ooms, G. Degiovanni, S. Morel, P. van der Bruggen, T. Boon, and B. Van den Eynde. 2004. An antigenic peptide produced by peptide splicing in the proteasome. Science 304:587-590. 2. Warren, E.H., N. Vigneron, M.A. Gavin, P.G. Coulie, V. Stroobant, A. Dalet, S.S. Tykodi, S.M. Xuereb, J.K. Mito, S.R. Riddell, and B.J. Van den Eynde. 2006. An antigen produced by splicing of noncontiguous peptides in the reverse order. Science 313:1444-1447. 3. Hanada, K., J.W. Yewdell, and J.C. Yang. 2004. Immune recognition of a human renal cancer antigen through post-translational protein splicing. Nature 427:252-256.
Van den Eynde, B. (2007). Invited lecture: Splicing of antigenic peptides by the proteasome. 3rd Charité Zeuthener See Workshop, Berlin, Germany. https://hdl.handle.net/2078.5/51425