ArticleNature communications2015
Transcriptional repression by the HDAC4-RelB-p52 complex regulates multiple myeloma survival and growth.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 60 citations in OpenAlex.
- Bcl-2 modifying factor (Bmf): "a mysterious stranger" in the Bcl-2 family proteins.Cell death and differentiation · 2026Review
- NF-κB RelB suppresses the inflammatory gene expression programs of dendritic cells by competing with RelA for binding to target gene promoters.Cell discovery · 2025Article
- ERRγ Promotes Multiple Myeloma Survival by Coordinating NF-κB Signaling and Mitochondrial Apoptosis Regulation.Oncology research · 2025Article
- Aberrant non-canonical NF-κB signalling reprograms the epigenome landscape to drive oncogenic transcriptomes in multiple myeloma.Nature communications · 2024Article
- Cytokine receptor IL27RA is an NF-κB-responsive gene involved in CD38 upregulation in multiple myeloma.Blood advances · 2023Article
- CUDC-101 as a dual-target inhibitor of EGFR and HDAC enhances the anti-myeloma effects of bortezomib by regulating G2/M cell cycle arrest.Journal of Zhejiang University. Science. B · 2023Article
- Role of NF-κB Signaling in the Interplay between Multiple Myeloma and Mesenchymal Stromal Cells.International journal of molecular sciences · 2023Review
- HDAC4 in cancer: A multitasking platform to drive not only epigenetic modifications.Frontiers in molecular biosciences · 2023Review
- Article
- Functional genetic screen identifies ITPR3/calcium/RELB axis as a driver of colorectal cancer metastatic liver colonization.Developmental cell · 2022Article
- The Prospective Application of Melatonin in Treating Epigenetic Dysfunctional Diseases.Frontiers in pharmacology · 2022Review
- Hyperglycemia-induced increasing ofAnnals of translational medicine · 2021Article
- E3 ligase c-Cbl regulates intestinal inflammation through suppressing fungi-induced noncanonical NF-κB activation.Science advances · 2021Article
- Potential Role of microRNAs in inducing Drug Resistance in Patients with Multiple Myeloma.Cells · 2021Review
- HDAC4 promotes nasopharyngeal carcinoma progression and serves as a therapeutic target.Cell death & disease · 2021Article
- Genome-wide identification of methylated CpG sites in nongenital cutaneous warts.BMC medical genomics · 2020Article
- 4-1BB costimulation promotes CAR T cell survival through noncanonical NF-κB signaling.Science signaling · 2020Article
- Dynein light chain binding determines complex formation and posttranslational stability of the Bcl-2 family members Bmf and Bim.Cell death and differentiation · 2020Article
- Frequent upregulation of G9a promotes RelB-dependent proliferation and survival in multiple myeloma.Experimental hematology & oncology · 2020Article
- HDAC4 Levels Control Sensibility toward Cisplatin in Gastric Cancer via the p53-p73/BIK Pathway.Cancers · 2019Article
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 3 countries.
Funding
Abstract
Although transcriptional activation by NF-κB is well appreciated, physiological importance of transcriptional repression by NF-κB in cancer has remained elusive. Here we show that an HDAC4-RelB-p52 complex maintains repressive chromatin around proapoptotic genes Bim and BMF and regulates multiple myeloma (MM) survival and growth. Disruption of RelB-HDAC4 complex by a HDAC4-mimetic polypeptide blocks MM growth. RelB-p52 also represses BMF translation by regulating miR-221 expression. While the NIK-dependent activation of RelB-p52 in MM has been reported, we show that regardless of the activation status of NIK and the oncogenic events that cause plasma cell malignancy, several genetically diverse MM cells including Bortezomib-resistant MM cells are addicted to RelB-p52 for survival. Importantly, RelB is constitutively phosphorylated in MM and ERK1 is a RelB kinase. Phospho-RelB remains largely nuclear and is essential for Bim repression. Thus, ERK1-dependent regulation of nuclear RelB is critical for MM survival and explains the NIK-independent role of RelB in MM.
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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.