ArticleThe EMBO journal2017
Tumor suppressor Tsc1 is a new Hsp90 co-chaperone that facilitates folding of kinase and non-kinase clients.
Article in The EMBO journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
63 citing papers in PubMed, 89 citations in OpenAlex.
- Insights into the function and structure of the R2TP (RUVBL1-RUVBL2-RPAP3-PIH1D1) chaperone complex.Cell stress & chaperones · 2026Review
- Identification and Integration of LRG1-Induced Differentially Expressed Gene (DEG) Hub Profiles in Breast Cancer Cells.International journal of molecular sciences · 2026Article
- Article
- c-KIT joins the TSC ToolKIT: a new driver of renal cystogenesis.EMBO molecular medicine · 2026Article
- The critical role of the proto-oncogene c-Kit in TSC renal cystogenesis.EMBO molecular medicine · 2026Article
- Primary and secondary pseudo-stability and progression after atezolizumab with and without bevacizumab.Journal for immunotherapy of cancer · 2026Article
- Demystifying programmed cell death in lung adenocarcinoma: combined prognostic model construction.Translational cancer research · 2025Article
- Advances in the structures, mechanisms and targeting of molecular chaperones.Signal transduction and targeted therapy · 2025Review
- Ordered ATP hydrolysis in the Hsp90 chaperone is regulated by Aha1 and a conserved post-translational modification.Protein science : a publication of the Protein Society · 2025Article
- Downregulation of PGAM2 alleviates angiotensin II-induced cardiac hypertrophy by destabilizing HSP90 and inactivating the mTOR/IKKα signaling pathway.International journal of biological sciences · 2025Article
- New insights into tuberous sclerosis complex: from structure to pathogenesis.Frontiers in cell and developmental biology · 2025Review
- SUMOylation of protein phosphatase 5 regulates phosphatase activity and substrate release.EMBO reports · 2024Article
- Evolution of the conformational dynamics of the molecular chaperone Hsp90.Nature communications · 2024Article
- Review
- Recruitment of Ahsa1 to Hsp90 is regulated by a conserved peptide that inhibits ATPase stimulation.EMBO reports · 2024Article
- Second international symposium on the chaperone code, 2023.Cell stress & chaperones · 2024Article
- The role of Aha1 in cancer and neurodegeneration.Frontiers in molecular neuroscience · 2024Review
- The role of molecular chaperones in the mechanisms of epileptogenesis.Cell stress & chaperones · 2023Review
- Saccharomyces cerevisiae as a tool for deciphering Hsp90 molecular chaperone function.Essays in biochemistry · 2023Article
- Activation of autophagy depends on Atg1/Ulk1-mediated phosphorylation and inhibition of the Hsp90 chaperone machinery.Cell reports · 2023Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
The tumor suppressors Tsc1 and Tsc2 form the tuberous sclerosis complex (TSC), a regulator of mTOR activity. Tsc1 stabilizes Tsc2; however, the precise mechanism involved remains elusive. The molecular chaperone heat-shock protein 90 (Hsp90) is an essential component of the cellular homeostatic machinery in eukaryotes. Here, we show that Tsc1 is a new co-chaperone for Hsp90 that inhibits its ATPase activity. The C-terminal domain of Tsc1 (998-1,164 aa) forms a homodimer and binds to both protomers of the Hsp90 middle domain. This ensures inhibition of both subunits of the Hsp90 dimer and prevents the activating co-chaperone Aha1 from binding the middle domain of Hsp90. Conversely, phosphorylation of Aha1-Y223 increases its affinity for Hsp90 and displaces Tsc1, thereby providing a mechanism for equilibrium between binding of these two co-chaperones to Hsp90. Our findings establish an active role for Tsc1 as a facilitator of Hsp90-mediated folding of kinase and non-kinase clients-including Tsc2-thereby preventing their ubiquitination and proteasomal degradation.
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What OpenQuestion holds
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.