ArticleGenes & development2010
Tel2 structure and function in the Hsp90-dependent maturation of mTOR and ATR complexes.
Article in Genes & development, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers.
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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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Who cites it
118 citing papers in PubMed, 183 citations in OpenAlex.
- Article
- Genomic dissection of hoof and leg conformation in Swiss dairy cattle populations reveals polygenic architecture and a recessive HYAL1 nonsense variant affecting longevity in Holstein cattle.Genetics, selection, evolution : GSE · 2026Article
- Insights into the function and structure of the R2TP (RUVBL1-RUVBL2-RPAP3-PIH1D1) chaperone complex.Cell stress & chaperones · 2026Review
- TELO2-interacting protein 1 (TTI1), a novel Wnt/β-catenin target gene, decreases chemo-sensitivity in colorectal cancer by modulating DNA damage responses.Molecular biomedicine · 2026Article
- Lennox-Gastaut syndrome in a patient with biallelic TELO2 variants.Epileptic disorders : international epilepsy journal with videotape · 2026Article
- A tti1 mutation in the Tel2-Tti1-Tti2 complex specifically eliminates the cellular function of Rad3ATR, but not that of other PIKKs in fission yeast.PLoS genetics · 2026Article
- RPAP3: Structural evolution, chaperone networks, and disease implications of a transcriptional Co-chaperone.The Journal of biological chemistry · 2026Review
- Co-translational determination of quaternary structures in chaperone factories.Nature communications · 2026Article
- Characterization of WAC interactions with R2TP and TTT chaperone complexes linking glucose and glutamine availability to mTORC1 activity.FEBS open bio · 2025Article
- Article
- The first Iranian patient with You-Hoover-Fong syndrome and a review of the literature on 27 cases: expanding the genotypic and phenotypic spectrum.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Review
- The mTORC2 signaling network: targets and cross-talks.The Biochemical journal · 2024Review
- Old and new strategies in therapy and diagnosis against fungal infections.Applied microbiology and biotechnology · 2024Review
- Maturation and Assembly of mTOR Complexes by the HSP90-R2TP-TTT Chaperone System: Molecular Insights and Mechanisms.Sub-cellular biochemistry · 2024Review
- The multi-faceted roles of R2TP complex span across regulation of gene expression, translation, and protein functional assembly.Biophysical reviews · 2023Review
- FACS-based genome-wide CRISPR screens define key regulators of DNA damage signaling pathways.Molecular cell · 2023Article
- Genome-scale mapping of DNA damage suppressors through phenotypic CRISPR-Cas9 screens.Molecular cell · 2023Article
- Hsp90 is a potential risk factor for ovarian cancer prognosis: an evidence of a Chinese clinical center.BMC cancer · 2023Article
- Exploring the Functional Roles of Telomere Maintenance 2 in the Tumorigenesis of Glioblastoma Multiforme and Drug Responsiveness to Temozolomide.International journal of molecular sciences · 2023Article
- TTT (Tel2-Tti1-Tti2) Complex, the Co-Chaperone of PIKKs and a Potential Target for Cancer Chemotherapy.International journal of molecular sciences · 2023Review
58 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
We reported previously that the stability of all mammalian phosphatidylinositol 3-kinase-related protein kinases (PIKKs) depends on their interaction with Tel2, the ortholog of yeast Tel2 and Caenorhabditis elegans Clk-2. Here we provide evidence that Tel2 acts with Hsp90 in the maturation of PIKK complexes. Quantitative immunoblotting showed that the abundance of Tel2 is low compared with the PIKKs, and Tel2 preferentially bound newly synthesized ATM, ATR, mTOR, and DNA-PKcs. Tel2 complexes contained, in addition to Tti1-Tti2, the Hsp90 chaperone, and inhibition of Hsp90 interfered with the interaction of Tel2 with the PIKKs. Analysis of in vivo labeled nascent protein complexes showed that Tel2 and Hsp90 mediate the formation of the mTOR TORC1 and TORC2 complexes and the association of ATR with ATRIP. The structure of yeast Tel2, reported here, shows that Tel2 consists of HEAT-like helical repeats that assemble into two separate α-solenoids. Through mutagenesis, we identify a surface patch of conserved residues involved in binding to the Tti1-Tti2 complex in vitro. In vivo, mutation of this conserved patch affects cell growth, levels of PIKKs, and ATM/ATR-mediated checkpoint signaling, highlighting the importance of Tti1-Tti2 binding to the function of Tel2. Taken together, our data suggest that the Tel2-Tti1-Tti2 complex is a PIKK-specific cochaperone for Hsp90.
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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.