Abstract
An alanyl-alanyl-phenylalanyl-7-amino-4-methylcoumarin-hydrolyzing protease particle copurifying with 26S proteasomes was isolated and identified as tripeptidyl peptidase II (TPPII), a cytosolic subtilisin-like peptidase of unknown function. The particle is larger than the 26S proteasome and has a rod-shaped, dynamic supramolecular structure. TPPII exhibits enhanced activity in proteasome inhibitor-adapted cells and degrades polypeptides by exo- as well as predominantly trypsin-like endoproteolytic cleavage. TPPII may thus participate in extralysosomal polypeptide degradation and may in part account for nonproteasomal epitope generation as postulated for certain major histocompatibility complex class I alleles. In addition, TPPII may be able to substitute for some metabolic functions of the proteasome.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcysteine / analogs & derivatives
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Acetylcysteine / pharmacology
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Alleles
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Amino Acid Chloromethyl Ketones / pharmacology
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Aminopeptidases
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Animals
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Cell Survival
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Coumarins / metabolism
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Cysteine Endopeptidases / metabolism*
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Cytosol / enzymology
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Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
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Epitopes / metabolism
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Genes, MHC Class I
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Hydrolysis
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Mice
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Molecular Weight
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Multienzyme Complexes / metabolism*
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Oligopeptides / metabolism
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Proteasome Endopeptidase Complex
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Serine Endopeptidases / chemistry
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Serine Endopeptidases / isolation & purification
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Serine Endopeptidases / metabolism*
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Serine Proteinase Inhibitors / pharmacology
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Substrate Specificity
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Tumor Cells, Cultured
Substances
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Amino Acid Chloromethyl Ketones
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Coumarins
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Epitopes
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Multienzyme Complexes
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Oligopeptides
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Serine Proteinase Inhibitors
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alanyl-alanyl-phenylalanyl-7-amino-4-methylcoumarin
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alanyl-alanyl-phenylalanine chloromethyl ketone
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lactacystin
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Aminopeptidases
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Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
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tripeptidyl-peptidase 2
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Serine Endopeptidases
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Cysteine Endopeptidases
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Proteasome Endopeptidase Complex
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Acetylcysteine