ArticleProceedings of the National Academy of Sciences of the United States of America2013
Hsp70/Hsp90 chaperone machinery is involved in the assembly of the purinosome.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 80 citations in OpenAlex.
- Exosomes in Alzheimer's disease: neuroinflammation mitigation via immune modulation and inflammatory pathway targeting.Molecular biology reports · 2026Review
- IMP metabolic mechanisms and IMPDH targeting strategies in tumor metabolic reprogramming and therapy (Review).International journal of molecular medicine · 2026Review
- Microcephaly-associated protein WDR62 supports purine metabolism by interacting with co-chaperone BAG2.The EMBO journal · 2026Article
- Article
- Enzyme Assemblies in Nucleotide Metabolism: Structure, Regulation, and Disease Implications.Advances in experimental medicine and biology · 2026Review
- Metabolic functions for molecular chaperones and stress proteins in microcephaly.Cellular and molecular life sciences : CMLS · 2025Review
- Synergistic Inhibition of PI3K and HSP90 Enhanced Antitumorigenic Efficacy in Adrenocortical Carcinoma.Research square · 2025Article
- Resilience and Vulnerabilities of Tumor Cells under Purine Shortage Stress.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Gene Expression Analysis of HPRT-Deficient Cells Maintained with Physiological Levels of Folic Acid.Cells · 2025Article
- Resilience and vulnerabilities of tumor cells under purine shortage stress.bioRxiv : the preprint server for biology · 2025Article
- Therapeutic targeting de novo purine biosynthesis driven by β-catenin-dependent PPAT upregulation in hepatoblastoma.Cell death & disease · 2025Article
- A high throughput assay for phosphoribosylformylglycinamidine synthase.SLAS discovery : advancing life sciences R & D · 2025Article
- Co-chaperones fine-tune the function of heat shock protein 70 (Hsp70), whether to fold, hold, or degrade substrates in ensuring cellular protein homeostasis.Journal of biosciences · 2025Review
- Purinosomes and Purine Metabolism in Mammalian Neural Development: A Review.Acta histochemica et cytochemica · 2024Review
- Interplay between mTOR and Purine Metabolism Enzymes and Its Relevant Role in Cancer.International journal of molecular sciences · 2024Review
- Cytoophidia: a conserved yet promising mode of enzyme regulation in nucleotide metabolism.Molecular biology reports · 2024Review
- A journey into the regulatory secrets of theFrontiers in pharmacology · 2024Review
- Chaperone regulation of biomolecular condensates.Frontiers in biophysics · 2024Article
- Regulatory mechanisms of one-carbon metabolism enzymes.The Journal of biological chemistry · 2023Review
- The roles of molecular chaperones in regulating cell metabolism.FEBS letters · 2023Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The de novo biosynthesis of purines is carried out by a highly conserved metabolic pathway that includes several validated targets for anticancer, immunosuppressant, and anti-inflammatory chemotherapeutics. The six enzymes in humans that catalyze the 10 chemical steps from phosphoribosylpyrophosphate to inosine monophosphate were recently shown to associate into a dynamic multiprotein complex called the purinosome. Here, we demonstrate that heat shock protein 90 (Hsp90), heat shock protein 70 (Hsp70), and several cochaperones functionally colocalize with this protein complex. Knockdown of expression levels of the identified cochaperones leads to disruption of purinosomes. In addition, small molecule inhibitors of Hsp90 and Hsp70 reversibly disrupt purinosomes and are shown to have a synergistic effect with methotrexate, an anticancer agent that targets purine biosynthesis. These data implicate the Hsp90/Hsp70 chaperone machinery in the assembly of the purinosome and provide a strategy for the development of improved anticancer therapies that disrupt purine biosynthesis.
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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.