ArticleEuropean journal of immunology2015
HSP90 inhibitors decrease AID levels and activity in mice and in human cells.
Article in European journal of immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 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
12 citing papers in PubMed, 18 citations in OpenAlex.
- Deaminase Modulation Driving a New Era in Drug Development.International journal of molecular sciences · 2025Review
- Synthesis and Biological Evaluation of PEGylated MWOMolecules (Basel, Switzerland) · 2022Article
- Structure-Based Design of First-Generation Small Molecule Inhibitors Targeting the Catalytic Pockets of AID, APOBEC3A, and APOBEC3B.ACS pharmacology & translational science · 2021Article
- Small Molecule Inhibitors of Activation-Induced Deaminase Decrease Class Switch Recombination in B Cells.ACS pharmacology & translational science · 2021Article
- AID in Chronic Lymphocytic Leukemia: Induction and Action During Disease Progression.Frontiers in oncology · 2021Review
- Interplay between UNG and AID governs intratumoral heterogeneity in mature B cell lymphoma.PLoS genetics · 2020Article
- The uracil-DNA glycosylase UNG protects the fitness of normal and cancer B cells expressing AID.NAR cancer · 2020Article
- Signaling control of antibody isotype switching.Advances in immunology · 2019Review
- Transcription factor YY1 can control AID-mediated mutagenesis in mice.European journal of immunology · 2018Article
- Mutations, kataegis and translocations in B cells: understanding AID promiscuous activity.Nature reviews. Immunology · 2016Review
- Pharmacological manipulation of AID.Oncotarget · 2015Article
- AIDing cancer treatment: Reducing AID activity via HSP90 inhibition.European journal of immunology · 2015Article
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
Activation induced deaminase (AID) initiates somatic hypermutation and class switch recombination of the Ig genes in antigen-activated B cells, underpinning antibody affinity maturation and isotype switching. AID can also be pathogenic by contributing to autoimmune diseases and oncogenic mutations. Moreover, AID can exert noncanonical functions when aberrantly expressed in epithelial cells. The lack of specific inhibitors prevents therapeutic applications to modulate AID functions. Here, we have exploited our previous finding that the HSP90 molecular chaperoning pathway stabilizes AID in B cells, to test whether HSP90 inhibitors could target AID in vivo. We demonstrate that chronic administration of HSP90 inhibitors decreases AID protein levels and isotype switching in immunized mice. HSP90 inhibitors also reduce disease severity in a mouse model of acute B-cell lymphoblastic leukemia in which AID accelerates disease progression. We further show that human AID protein levels are sensitive to HSP90 inhibition in normal and leukemic B cells, and that HSP90 inhibition prevents AID-dependent epithelial to mesenchymal transition in a human breast cancer cell line in vitro. Thus, we provide proof-of-concept that HSP90 inhibitors indirectly target AID in vivo and that endogenous human AID is widely sensitive to them, which could have therapeutic applications.
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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.