ArticleProceedings of the National Academy of Sciences of the United States of America2000
Integration of the ubiquitin-proteasome pathway with a cytosolic oligopeptidase activity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 114 citations in OpenAlex.
- Perturbation of multiprotein complexes in skeletal muscle induces protective proteases in the CNS that degrade pathogenic proteins.npj aging · 2025Article
- An adaptive stress response that confers cellular resilience to decreased ubiquitination.Nature communications · 2023Article
- Modulation of protease expression by the transcription factor Ptx1/PITX regulates protein quality control during aging.Cell reports · 2023Article
- Contribution of proteases to the hallmarks of aging and to age-related neurodegeneration.Aging cell · 2022Review
- Proteasome stress in skeletal muscle mounts a long-range protective response that delays retinal and brain aging.Cell metabolism · 2021Article
- Alternative Antigen Processing for MHC Class I: Multiple Roads Lead to Rome.Frontiers in immunology · 2015Review
- Tripeptidyl peptidase II regulates sperm function by modulating intracellular Ca(2+) stores via the ryanodine receptor.PloS one · 2013Article
- Tripeptidyl Peptidase II Is Required for c-MYC-Induced Centriole Overduplication and a Novel Therapeutic Target in c-MYC-Associated Neoplasms.Genes & cancer · 2010Article
- The Enigma of Tripeptidyl-Peptidase II: Dual Roles in Housekeeping and Stress.Journal of oncology · 2010Article
- Proteases in MHC class I presentation and cross-presentation.Journal of immunology (Baltimore, Md. : 1950) · 2010Review
- Analysis of the role of tripeptidyl peptidase II in MHC class I antigen presentation in vivo.Journal of immunology (Baltimore, Md. : 1950) · 2009Article
- Chronic ethanol feeding affects proteasome-interacting proteins.Proteomics · 2009Article
- Article
- Activation of cellular death programs associated with immunosenescence-like phenotype in TPPII knockout mice.Proceedings of the National Academy of Sciences of the United States of America · 2008Article
- Structure of aminopeptidase N from Escherichia coli suggests a compartmentalized, gated active site.Proceedings of the National Academy of Sciences of the United States of America · 2006Article
- Molecular architecture and assembly mechanism of Drosophila tripeptidyl peptidase II.Proceedings of the National Academy of Sciences of the United States of America · 2005Article
- The ubiquitin-proteasome system as a drug target in cerebrovascular disease: therapeutic potential of proteasome inhibitors.Current opinion in investigational drugs (London, England : 2000) · 2005Review
- Generation of major histocompatibility complex class I antigens: functional interplay between proteasomes and TPPII.Nature immunology · 2004Review
- Voltage sensor mutations differentially target misfolded K+ channel subunits to proteasomal and non-proteasomal disposal pathways.FEBS letters · 2004Article
- Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.