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Integration of the ubiquitin-proteasome pathway with a cytosolic oligopeptidase activity

Academic Article
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Overview

authors

  • Wang, E. W.
  • Kessler, B. M.
  • Borodovsky, A.
  • Cravatt, Benjamin
  • Bogyo, M.
  • Ploegh, H. L.
  • Glas, R.

publication date

  • August 2000

journal

  • Proceedings of the National Academy of Sciences of the United States of America  Journal

abstract

  • Cytosolic proteolysis is carried out predominantly by the proteasome. We show that a large oligopeptidase, tripeptidylpeptidase II (TPPII), can compensate for compromised proteasome activity. Overexpression of TPPII is sufficient to prevent accumulation of polyubiquitinated proteins and allows survival of EL-4 cells at otherwise lethal concentrations of the covalent proteasome inhibitor NLVS (NIP-leu-leu-leu-vinylsulfone). Elevated TPPII activity also partially restores peptide loading of MHC molecules. Purified proteasomes from adapted cells lack the chymotryptic-like activity, but still degrade longer peptide substrates via residual activity of their Z subunits. However, growth of adapted cells depends on induction of other proteolytic activities. Therefore, cytosolic oligopeptidases such as TPPII normalize rates of intracellular protein breakdown required for normal cellular function and viability.

subject areas

  • Amino Acid Sequence
  • Animals
  • Caspases
  • Cysteine Endopeptidases
  • Cytosol
  • Histocompatibility Antigens Class I
  • Kinetics
  • Lymphoma
  • Mice
  • Molecular Sequence Data
  • Multienzyme Complexes
  • Peptide Fragments
  • Peptide Hydrolases
  • Proteasome Endopeptidase Complex
  • Recombinant Proteins
  • Substrate Specificity
  • Transfection
  • Trypsin
  • Tumor Cells, Cultured
  • Ubiquitins
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Identity

PubMed Central ID

  • PMC27648

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.180328897

PubMed ID

  • 10954757
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Additional Document Info

start page

  • 9990

end page

  • 9995

volume

  • 97

issue

  • 18

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