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

Journal article

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...

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Authors: Wang, E; Kessler, B; Borodovsky, A; Cravatt, B; Bogyo, M

• Publication status: Published
• Journal: Proceedings of the National Academy of Sciences of the United States of America
• Volume: 97
• Issue: 18
• Pages: 9990-9995
• Publication date: 2000-08-01
• DOI: 10.1073/pnas.180328897
• EISSN: 1091-6490
• ISSN: 0027-8424
• Language: English
• Keywords: Animals; Molecular Sequence Data; Lymphoma; Proteasome Endopeptidase Complex; Cytosol; Multienzyme Complexes; Transfection; Cysteine Endopeptidases; Ubiquitins; Caspases; Mice; Tumor Cells, Cultured; Kinetics; Recombinant Proteins; Peptide Fragments; Trypsin; Peptide Hydrolases; Substrate Specificity; Amino Acid Sequence; Histocompatibility Antigens Class I