ArticleThe EMBO journal2007
Puromycin-sensitive aminopeptidase is the major peptidase responsible for digesting polyglutamine sequences released by proteasomes during protein degradation.
Article in The EMBO journal, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.
- Systematic Review and Meta-Analyses of Aminopeptidases as Prognostic Biomarkers in Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2023Pooled it
- Pharmacological effect of quinazoline-2,4(1H,3H)-dione derivatives: a review.Molecular diversity · 2026Review
- Perturbation of multiprotein complexes in skeletal muscle induces protective proteases in the CNS that degrade pathogenic proteins.npj aging · 2025Article
- Article
- Modulation of endogenous opioid signaling by inhibitors of puromycin-sensitive aminopeptidase.European journal of medicinal chemistry · 2024Article
- Modulation of endogenous opioid signaling by inhibitors of puromycin sensitive aminopeptidase.bioRxiv : the preprint server for biology · 2024Article
- Proteome and Peptidome Changes and Zn Concentration in Chicken after In Ovo Stimulation with a Multi-Strain Probiotic and Zn-Gly Chelate: Preliminary Research.Current issues in molecular biology · 2024Article
- Modulation of protease expression by the transcription factor Ptx1/PITX regulates protein quality control during aging.Cell reports · 2023Article
- Article
- Molecular Pathophysiological Mechanisms in Huntington's Disease.Biomedicines · 2022Review
- Contribution of proteases to the hallmarks of aging and to age-related neurodegeneration.Aging cell · 2022Review
- PSA controls hepatic lipid metabolism by regulating the NRF2 signaling pathway.Journal of molecular cell biology · 2021Article
- Comparative proteomics reveals new insights into the endosperm responses to drought, salinity and submergence in germinating wheat seeds.Plant molecular biology · 2021Article
- Association between the Microsatellite Ap243, AC117 and SV185 Polymorphisms andVeterinary sciences · 2020Article
- Novel progressive acrodysostosis-like skeletal dysplasia, cerebellar atrophy, and ichthyosis.American journal of medical genetics. Part A · 2020Article
- Comprehensive Transcriptome Analysis Reveals Insights into Phylogeny and Positively Selected Genes ofAnimals : an open access journal from MDPI · 2020Article
- The science of puromycin: From studies of ribosome function to applications in biotechnology.Computational and structural biotechnology journal · 2020Review
- Proteomic and Transcriptomic Profiling Identifies Early Developmentally Regulated Proteins inCells · 2019Article
- Circadian gene variants and the skeletal muscle circadian clock contribute to the evolutionary divergence in longevity acrossGenome research · 2019Article
- Proteins of the Nucleolus ofCells · 2019Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Long stretches of glutamine (Q) residues are found in many cellular proteins. Expansion of these polyglutamine (polyQ) sequences is the underlying cause of several neurodegenerative diseases (e.g. Huntington's disease). Eukaryotic proteasomes have been found to digest polyQ sequences in proteins very slowly, or not at all, and to release such potentially toxic sequences for degradation by other peptidases. To identify these key peptidases, we investigated the degradation in cell extracts of model Q-rich fluorescent substrates and peptides containing 10-30 Q's. Their degradation at neutral pH was due to a single aminopeptidase, the puromycin-sensitive aminopeptidase (PSA, cytosol alanyl aminopeptidase). No other known cytosolic aminopeptidase or endopeptidase was found to digest these polyQ peptides. Although tripeptidyl peptidase II (TPPII) exhibited limited activity, studies with specific inhibitors, pure enzymes and extracts of cells treated with siRNA for TPPII or PSA showed PSA to be the rate-limiting activity against polyQ peptides up to 30 residues long. (PSA digests such Q sequences, shorter ones and typical (non-repeating) peptides at similar rates.) Thus, PSA, which is induced in neurons expressing mutant huntingtin, appears critical in preventing the accumulation of polyQ peptides in normal cells, and its activity may influence susceptibility to polyQ diseases.
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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.