title: Substrate specificity of the human proteasome.
abstract: BACKGROUND
  Regulated proteolysis by the proteasome is crucial for a broad array of cellular processes, from control of the cell cycle to production of antigens.
  
  
  RESULTS
  The rules governing the N-terminal primary and extended substrate specificity of the human 20S proteasome in the presence or absence of 11S proteasome activators (REGalpha/beta and REGgamma) have been elaborated using activity-based proteomic library tools.
  
  
  CONCLUSIONS
  The 11S proteasome activators are shown to be important for both increasing the activity of the 20S proteasome and for altering its cleavage pattern and substrate specificity. These data also establish that the extended substrate specificity is an important factor for proteasomal cleavage. The specificities observed have features in common with major histocompatibility complex (MHC) class I ligands and can be used to improve the prediction of MHC class I restricted cytotoxic T-cell responses.
authors.affiliation: Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA. harris@gnf.org
authors.forename: J L
authors.initials: JL
authors.lastname: Harris
authors.forename: P B
authors.initials: PB
authors.lastname: Alper
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: M
authors.initials: M
authors.lastname: Rechsteiner
authors.forename: B J
authors.initials: BJ
authors.lastname: Backes
mesh_terms: D000595:Amino Acid Sequence; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004789:Enzyme Activation; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism*; D019151:Peptide Library; D046988:Proteasome Endopeptidase Complex; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D015395:Histocompatibility Antigens Class I; D008024:Ligands; D009097:Multienzyme Complexes; D019151:Peptide Library; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex