ArticleNature communications2024
Super enhancer acquisition drives expression of oncogenic PPP1R15B that regulates protein homeostasis in multiple myeloma.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Translocation-induced enhancer rewiring reveals cryptic oncogenic circuits in multiple myeloma.Science advances · 2026Article
- DNMT3A/TET2-mediated epigenetic alteration in Type-1 diabetes dysregulates the haematopoiesis.Molecular biology reports · 2026Review
- Spatiotemporal activation of unfolded protein response by combined sonodynamic therapy and proteasome inhibition with bortezomib-conjugated TiN nanoparticles.Bioactive materials · 2026Article
- Schlafen 11 Is Overexpressed in Multiple Myeloma and Undergoes Nucleolar Translocation in Response to Bortezomib.Cancer research communications · 2026Article
- Transcription factor 19 modulates fatty acid elongation and unfolded protein response to attenuate palmitic acid-induced hepatic dysfunction.Nature communications · 2026Article
- Article
- Targeting PRKCN, an Essential Driver Orchestrating mTOR-IRF4 Axis Independently of Kinase Activity, in Multiple Myeloma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Super-Enhancer-Driven SOX4/SMAD3 Mediate Membrane Remodeling by Regulating Phospholipid Metabolism to Accelerate Leukemia Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Schlafen 11 (SLFN11) overexpression and nucleolar localization in response to bortezomib in multiple myeloma.bioRxiv : the preprint server for biology · 2026Article
- Single-cell profiling uncovers extracellular vesicle-associated malignant plasma cell subpopulations driving multiple myeloma progression.Frontiers in immunology · 2026Article
- Nuclear respiratory factor 1 promotes cell survival in multiple myeloma under proteasome inhibition therapy.Blood · 2025Article
- CHIP and aging: a key regulator of proteostasis and cellular senescence.Biogerontology · 2025Review
- Protein serine/threonine phosphatases in tumor microenvironment: a vital player and a promising therapeutic target.Theranostics · 2025Review
- Super enhancer acquisition drives expression of oncogenic PPP1R15B that regulates protein homeostasis in multiple myeloma.Nature communications · 2024Article
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Authors and funding
12 authors.
Funding
Abstract
Multiple myeloma is a hematological malignancy arising from immunoglobulin-secreting plasma cells. It remains poorly understood how chromatin rewiring of regulatory elements contributes to tumorigenesis and therapy resistance in myeloma. Here we generate a high-resolution contact map of myeloma-associated super-enhancers by integrating H3K27ac ChIP-seq and HiChIP from myeloma cell lines, patient-derived myeloma cells and normal plasma cells. Our comprehensive transcriptomic and phenomic analyses prioritize candidate genes with biological and clinical implications in myeloma. We show that myeloma cells frequently acquire SE that transcriptionally activate an oncogene PPP1R15B, which encodes a regulatory subunit of the holophosphatase complex that dephosphorylates translation initiation factor eIF2α. Epigenetic silencing or knockdown of PPP1R15B activates pro-apoptotic eIF2α-ATF4-CHOP pathway, while inhibiting protein synthesis and immunoglobulin production. Pharmacological inhibition of PPP1R15B using Raphin1 potentiates the anti-myeloma effect of bortezomib. Our study reveals that myeloma cells are vulnerable to perturbation of PPP1R15B-dependent protein homeostasis, highlighting a promising therapeutic strategy.
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