Cancer Institute A national cancer institute
designated cancer center

Matthew Bogyo

Publication Details

  • Integration of the ubiquitin-proteasome pathway with a cytosolic oligopeptidase activity PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Wang, E. W., Kessler, B. M., Borodovsky, A., Cravatt, B. F., Bogyo, M., Ploegh, H. L., Glas, R. 2000; 97 (18): 9990-9995


    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.

    View details for Web of Science ID 000089067500034

    View details for PubMedID 10954757

Stanford Medicine Resources:

Footer Links: