A giant protease with potential to substitute for some functions of the proteasome

Science. 1999 Feb 12;283(5404):978-81. doi: 10.1126/science.283.5404.978.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / analogs & derivatives
  • Acetylcysteine / pharmacology
  • Alleles
  • Amino Acid Chloromethyl Ketones / pharmacology
  • Aminopeptidases
  • Animals
  • Cell Survival
  • Coumarins / metabolism
  • Cysteine Endopeptidases / metabolism*
  • Cytosol / enzymology
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
  • Epitopes / metabolism
  • Genes, MHC Class I
  • Hydrolysis
  • Mice
  • Molecular Weight
  • Multienzyme Complexes / metabolism*
  • Oligopeptides / metabolism
  • Proteasome Endopeptidase Complex
  • Serine Endopeptidases / chemistry
  • Serine Endopeptidases / isolation & purification
  • Serine Endopeptidases / metabolism*
  • Serine Proteinase Inhibitors / pharmacology
  • Substrate Specificity
  • Tumor Cells, Cultured

Substances

  • Amino Acid Chloromethyl Ketones
  • Coumarins
  • Epitopes
  • Multienzyme Complexes
  • Oligopeptides
  • Serine Proteinase Inhibitors
  • alanyl-alanyl-phenylalanyl-7-amino-4-methylcoumarin
  • alanyl-alanyl-phenylalanine chloromethyl ketone
  • lactacystin
  • Aminopeptidases
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
  • tripeptidyl-peptidase 2
  • Serine Endopeptidases
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex
  • Acetylcysteine