ArticleMolecular and cellular biology2013
Large FK506-binding proteins shape the pharmacology of rapamycin.
Article in Molecular and cellular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 136 citations in OpenAlex.
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- Rapamycin reduces peritendinous fibrosis but has a limited effect on intratendinous healing in a rodent Achilles tendon injury model.Scientific reports · 2026Article
- Dissecting the Dual Drug Candidates Against Glioblastoma and Oligodendroglioma Through Integrated Transcriptome Analysis and Virtual Screening.Cell biochemistry and biophysics · 2025Article
- Decoding the anti-thrombotic effects of leonurine: a multimodal approach combining TCM repositioning and mTOR signaling.Chinese medicine · 2025Article
- Accommodating Statistical and Physics-Based Computational Protocols for Molecular Glue Model and Evaluation.Journal of chemical information and modeling · 2025Article
- Nondegradative Synthetic Molecular Glues Enter the Clinic.ChemMedChem · 2025Review
- Development of an FKBP12-recruiting chemical-induced proximity DNA-encoded library and its application to discover an autophagy potentiator.Cell chemical biology · 2025Article
- A peptide-centric local stability assay enables proteome-scale identification of the protein targets and binding regions of diverse ligands.Nature methods · 2025Article
- In silico identification of novel ligands targeting stress-related human FKBP5 protein in mental disorders.PloS one · 2025Article
- Molecular dynamics and experimental evaluation of piperine as a potential mTOR inhibitor in colon cancer cells.In silico pharmacology · 2025Article
- Mechanisms of Rehmannioside A Against Systemic Lupus Erythematosus Based on Network Pharmacology, Molecular Docking and Molecular Dynamics Simulation.Cell biochemistry and biophysics · 2024Article
- Molecular chameleons in drug discovery.Nature reviews. Chemistry · 2024Review
- Ceg1 depletion reveals mechanisms governing degradation of non-capped RNAs in Saccharomyces cerevisiae.Communications biology · 2023Article
- Screening the possible anti-cancer constituents of Hibiscus rosa-sinensis flower to address mammalian target of rapamycin: an in silico molecular docking, HYDE scoring, dynamic studies, and pharmacokinetic prediction.Molecular diversity · 2023Article
- Unbiased evaluation of rapamycin's specificity as an mTOR inhibitor.Aging cell · 2023Article
- Discovery of potential mTOR inhibitors from Cichorium intybus to find new candidate drugs targeting the pathological protein related to the breast cancer: an integrated computational approach.Molecular diversity · 2023Article
- Analysis of the Selective Antagonist SAFit2 as a Chemical Probe for the FK506-Binding Protein 51.ACS pharmacology & translational science · 2023Review
- Dissecting regulatory T cell expansion using polymer microparticles presenting defined ratios of self-antigen and regulatory cues.Frontiers in bioengineering and biotechnology · 2023Article
- Rapalogs downmodulate intrinsic immunity and promote cell entry of SARS-CoV-2.The Journal of clinical investigation · 2022Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The immunosuppressant and anticancer drug rapamycin works by inducing inhibitory protein complexes with the kinase mTOR, an important regulator of growth and proliferation. The obligatory accessory partner of rapamycin is believed to be FK506-binding protein 12 (FKBP12). Here we show that rapamycin complexes of larger FKBP family members can tightly bind to mTOR and potently inhibit its kinase activity. Cocrystal structures with FKBP51 and FKBP52 reveal the modified molecular binding mode of these alternative ternary complexes in detail. In cellular model systems, FKBP12 can be functionally replaced by larger FKBPs. When the rapamycin dosage is limiting, mTOR inhibition of S6K phosphorylation can be enhanced by FKBP51 overexpression in mammalian cells, whereas FKBP12 is dispensable. FKBP51 could also enable the rapamycin-induced hyperphosphorylation of Akt, which depended on higher FKBP levels than rapamycin-induced inhibition of S6K phosphorylation. These insights provide a mechanistic rationale for preferential mTOR inhibition in specific cell or tissue types by engaging specific FKBP homologs.
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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.