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Coordinated Dual Cleavages Induced by the Proteasome Regulator PA28 Lead to Dominant MHC Ligands
- Source :
- Cell. 86(2):253-262
- Publication Year :
- 1996
- Publisher :
- Elsevier BV, 1996.
-
Abstract
- The eukaryotic 20S proteasome is known to associate with the IFNγ-inducible regulator PA28. We analyzed the kinetics of product generation by 20S proteasomes with and without PA28. In the absence of PA28, the 20S proteasome rapidly generates peptides that have been cleaved only once, while internal fragments accumulate only slowly. In the presence of PA28, products generated by two flanking cleavages appear immediately as main products while the generation of single-cleavage products is strongly reduced. Kinetic data support a PA28-induced, coordinated double-cleavage mechanism. In particular, degradation of peptides derived from mouse cytomegalovirus pp89 and JAK1 kinase in the presence of PA28 leads to strongly enhanced production of the respective major histocompatibility complex ligands and potential precursors. These results show that PA28 profoundly alters the cleavage mechanism of the proteasome and appears to optimize the generation of dominant T-cell epitopes.
- Subjects :
- Proteasome Endopeptidase Complex
Placenta
T-Lymphocytes
Kinetics
Molecular Sequence Data
Regulator
Muscle Proteins
Biology
Cleavage (embryo)
Major histocompatibility complex
Ligands
Autoantigens
General Biochemistry, Genetics and Molecular Biology
Epitope
Mass Spectrometry
Substrate Specificity
Epitopes
Mice
Jak1 Kinase
Pregnancy
Histocompatibility Antigens
Animals
Humans
Amino Acid Sequence
Peptide sequence
Chromatography, High Pressure Liquid
Biochemistry, Genetics and Molecular Biology(all)
Proteins
Fibroblasts
Cell biology
Proteasome
Biochemistry
biology.protein
Female
Peptides
Subjects
Details
- ISSN :
- 00928674
- Volume :
- 86
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Cell
- Accession number :
- edsair.doi.dedup.....53cb56ccdc75480ff9cc633e5fc3a11c
- Full Text :
- https://doi.org/10.1016/s0092-8674(00)80097-5