ArticleBlood2013
Targeting the Hsp90-associated viral oncoproteome in gammaherpesvirus-associated malignancies.
Article in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
48 citing papers in PubMed, 74 citations in OpenAlex.
- First-in-human study of the epichaperome inhibitor PU-H71: clinical results and metabolic profile.Investigational new drugs · 2018Trial
- Targeting HSP90 in cancer: advances in the development of inhibitors, mechanisms of action, and therapeutic applications.Molecular cancer · 2026Review
- Inhibiting HSP27 activates the XBP1s/CerS1 interplay, which triggers DRP1-driven mitophagy, thereby protecting against cell death and promoting the KSHV lytic cycle in primary effusion lymphoma cells.Cell death discovery · 2026Article
- Modulators of the Hop-HSP90 Protein-Protein Interaction Disrupt KSHV Lytic Replication.ACS infectious diseases · 2024Article
- Hsp70-Hsp90 organising protein (HOP/STIP1) is required for KSHV lytic replication.The Journal of general virology · 2024Article
- Molecular Mechanisms of Kaposi Sarcoma-Associated Herpesvirus (HHV8)-Related Lymphomagenesis.Cancers · 2024Review
- Article
- Systems-level analyses of protein-protein interaction network dysfunctions via epichaperomics identify cancer-specific mechanisms of stress adaptation.Nature communications · 2023Article
- Targeting stressor-induced dysfunctions in protein-protein interaction networks via epichaperomes.Trends in pharmacological sciences · 2023Review
- Cancers associated with human gammaherpesviruses.The FEBS journal · 2022Review
- The penalty of stress - Epichaperomes negatively reshaping the brain in neurodegenerative disorders.Journal of neurochemistry · 2021Review
- Small-molecule inhibitor targeting the Hsp70-Bim protein-protein interaction in CML cells overcomes BCR-ABL-independent TKI resistance.Leukemia · 2021Article
- Chemical tools for epichaperome-mediated interactome dysfunctions of the central nervous system.Nature communications · 2021Article
- Proteomic approaches to investigate gammaherpesvirus biology and associated tumorigenesis.Advances in virus research · 2021Review
- Modulation of virus-induced NF-κB signaling by NEMO coiled coil mimics.Nature communications · 2020Article
- A Chemical Biology Approach to the Chaperome in Cancer-HSP90 and Beyond.Cold Spring Harbor perspectives in biology · 2020Review
- Chaperome Networks - Redundancy and Implications for Cancer Treatment.Advances in experimental medicine and biology · 2020Review
- Chaperome heterogeneity and its implications for cancer study and treatment.The Journal of biological chemistry · 2019Review
- Kaposi sarcoma.Nature reviews. Disease primers · 2019Review
- Article
Corrections and comments
- Commented on by
Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
PU-H71 is a purine-scaffold Hsp90 inhibitor that, in contrast to other Hsp90 inhibitors, displays unique selectivity for binding the fraction of Hsp90 that is preferentially associated with oncogenic client proteins and enriched in tumor cells (teHsp90). This property allows PU-H71 to potently suppress teHsp90 without inducing toxicity in normal cells. We found that lymphoma cells infected by Epstein-Barr virus or Kaposi sarcoma-associated herpes virus (KSHV) are exquisitely sensitive to this compound. Using PU-H71 affinity capture and proteomics, an unbiased approach to reveal oncogenic networks, we identified the teHsp90 interactome in KSHV(+) primary effusion lymphoma cells. Viral and cellular proteins were identified, including many involved in nuclear factor (NF)-κB signaling, apoptosis, and autophagy. KSHV vFLIP is a viral oncoprotein homologous to cFLIPs, with NF-κB-activating and antiapoptotic activities. We show that teHsp90 binds vFLIP but not cFLIPs. Treatment with PU-H71 induced degradation of vFLIP and IKKγ, NF-κB downregulation, apoptosis and autophagy in vitro, and more importantly, tumor responses in mice. Analysis of the interactome revealed apoptosis as a central pathway; therefore, we tested a BCL2 family inhibitor in primary effusion lymphoma cells. We found strong activity and synergy with PU-H71. Our findings demonstrate PU-H71 affinity capture identifies actionable networks that may help design rational combinations of effective therapies.
Indexed as
Identifiers
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.