title: A giant protease with potential to substitute for some functions of the proteasome.
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.
authors.affiliation: Max-Planck Institute of Immunobiology, Stübeweg 51, D-79108 Freiburg, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Geier
authors.forename: G
authors.initials: G
authors.lastname: Pfeifer
authors.forename: M
authors.initials: M
authors.lastname: Wilm
authors.forename: M
authors.initials: M
authors.lastname: Lucchiari-Hartz
authors.forename: W
authors.initials: W
authors.lastname: Baumeister
authors.forename: K
authors.initials: K
authors.lastname: Eichmann
authors.forename: G
authors.initials: G
authors.lastname: Niedermann
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D000483:Alleles; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000626:Aminopeptidases; D000818:Animals; D002470:Cell Survival; D003374:Coumarins / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D003600:Cytosol / Q000201:enzymology; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D000939:Epitopes / Q000378:metabolism; D005805:Genes, MHC Class I; D006868:Hydrolysis; D051379:Mice; D008970:Molecular Weight; D009097:Multienzyme Complexes / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D012697:Serine Endopeptidases / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured