ArticleCell reports2023
Modulation of protease expression by the transcription factor Ptx1/PITX regulates protein quality control during aging.
Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 20 citations in OpenAlex.
- UBA1 knockdown dysregulates UBA1-sensitive proteins and impairs muscle function in models of spinal muscular atrophy X-linked 2.Disease models & mechanisms · 2026Article
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- Intracellular Aβ42 Sequestration by a Serine Protease Mitigates Neurotoxicity in a Drosophila Alzheimer's Disease Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Perturbation of multiprotein complexes in skeletal muscle induces protective proteases in the CNS that degrade pathogenic proteins.npj aging · 2025Article
- Article
- The ubiquitin-conjugating enzyme UBE2D maintains a youthful proteome and ensures protein quality control during aging by sustaining proteasome activity.PLoS biology · 2025Article
- Transgenic sensors reveal compartment-specific effects of aggregation-prone proteins on subcellular proteostasis during aging.Cell reports methods · 2024Article
- Mutant GGGGCC RNA prevents YY1 from binding to Fuzzy promoter which stimulates Wnt/β-catenin pathway in C9ALS/FTD.Nature communications · 2023Article
- PROTAC-Based Protein Degradation as a Promising Strategy for Targeted Therapy in Sarcomas.International journal of molecular sciences · 2023Review
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Protein quality control is important for healthy aging and is dysregulated in age-related diseases. The autophagy-lysosome and ubiquitin-proteasome are key for proteostasis, but it remains largely unknown whether other proteolytic systems also contribute to maintain proteostasis during aging. Here, we find that expression of proteolytic enzymes (proteases/peptidases) distinct from the autophagy-lysosome and ubiquitin-proteasome systems declines during skeletal muscle aging in Drosophila. Age-dependent protease downregulation undermines proteostasis, as demonstrated by the increase in detergent-insoluble poly-ubiquitinated proteins and pathogenic huntingtin-polyQ levels in response to protease knockdown. Computational analyses identify the transcription factor Ptx1 (homologous to human PITX1/2/3) as a regulator of protease expression. Consistent with this model, Ptx1 protein levels increase with aging, and Ptx1 RNAi counteracts the age-associated downregulation of protease expression. Moreover, Ptx1 RNAi improves muscle protein quality control in a protease-dependent manner and extends lifespan. These findings indicate that proteases and their transcriptional modulator Ptx1 ensure proteostasis during aging.
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