ArticleCell death & disease2019
Inhibition of the BET family reduces its new target gene IDO1 expression and the production of L-kynurenine.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 25 citations in OpenAlex.
- Article
- IDO1 inhibition enhances CLDN18.2-CAR-T cell therapy in gastrointestinal cancers by overcoming kynurenine-mediated metabolic suppression in the tumor microenvironment.Journal of translational medicine · 2025Article
- A combinatorial screening protocol for identifying novel and highly potent dual-target inhibitor of BRD4 and STAT3 for kidney cancer therapy.Frontiers in pharmacology · 2025Article
- SNORA28 Promotes Proliferation and Radioresistance in Colorectal Cancer Cells through the STAT3 Pathway by Increasing H3K9 Acetylation in the LIFR Promoter.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
- Mutation of Basic Residues R283, R286, and K288 in the Matrix Protein of Newcastle Disease Virus Attenuates Viral Replication and Pathogenicity.International journal of molecular sciences · 2023Article
- BET inhibition triggers antitumor immunity by enhancing MHC class I expression in head and neck squamous cell carcinoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- TNKS inhibitors potentiate proliferative inhibition of BET inhibitors via reducing β-Catenin in colorectal cancer cells.American journal of cancer research · 2022Article
- Immunosuppressive network promotes immunosenescence associated with aging and chronic inflammatory conditions.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Are BET Inhibitors yet Promising Latency-Reversing Agents for HIV-1 Reactivation in AIDS Therapy?Viruses · 2021Review
- Cell-Based Identification of New IDO1 Modulator Chemotypes.Angewandte Chemie (International ed. in English) · 2021Article
- The BET family in immunity and disease.Signal transduction and targeted therapy · 2021Review
- Mechanism Exploration on the Immunoregulation of Allogeneic Heart Transplantation Rejection in Rats With Exosome miRNA and Proteins From Overexpressed IDO1 BMSCs.Cell transplantationArticle
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The bromodomain and extra terminal domain (BET) family members, including BRD2, BRD3, and BRD4, act as epigenetic readers to regulate gene expression. Indoleamine 2,3-dioxygenase 1 (IDO1) is an enzyme that participates in tumor immune escape primarily by catalyzing tryptophan to L-kynurenine. Here, we report that IDO1 is a new target gene of the BET family. RNA profiling showed that compound 9, a new BET inhibitor, reduced IDO1 mRNA up to seven times in Ty-82 cells. IDO1 differentially expressed in tumor cells and its expression could be induced with interferon gamma (IFN-γ). BET inhibitors (ABBV-075, JQ1, and OTX015) inhibited both constitutive and IFN-γ-inducible expression of IDO1. Similarly, reduction of BRD2, BRD3, or BRD4 decreased IDO1 expression. All these BET family members bound to the IDO1 promoter via the acetylated histone H3. JQ1 led to their release and reduced enrichment of RNA polymerase II (Pol II) on the promoter. IFN-γ increased the binding of BRD2, BRD3, BRD4, and Pol II on the IDO1 promoter by increasing the acetylation of histone H3, which could be prevented by JQ1 partially or even completely. Furthermore, both JQ1 and OTX015 decreased the production of L-kynurenine. The combination of BET inhibitors with the IDO1 inhibitor further reduced L-kynurenine, though only marginally. Importantly, the BET inhibitor ABBV-075 significantly inhibited the growth of human Ty-82 xenografts in nude mice and reduced both protein and mRNA levels of IDO1 in the xenografts. This finding lays a basis for the potential combination of BET inhibitors and IDO1 inhibitors for the treatment of IDO1-expressing cancers.
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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.