ArticleNature cell biology2023
PBRM1-deficient PBAF complexes target aberrant genomic loci to activate the NF-κB pathway in clear cell renal cell carcinoma.
Article in Nature cell biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- LSD1 Promotes Immune Exclusion and Suppresses IFN-γ-Associated Transcriptional Programs in Triple-Negative Breast Cancer.Cancers · 2026Article
- The roles of chromatin remodeling and 3D genome organization in cancers: from mechanistic insights to emerging treatment options.Molecular cancer · 2026Review
- PBRM1-dependent PBAF targeting is required for EMT and metastasis in breast cancer.Science advances · 2026Article
- Synthetic lethality between PBRM1 deficiency and PARP inhibitors: exploiting G2/M checkpoint arrest in colorectal cancer.Molecular medicine (Cambridge, Mass.) · 2026Article
- Implications for clinical prognosis and target discovery of the SWI/SNF complex in genitourinary tumors.Discover oncology · 2026Review
- Integrative multi-omic analysis identifies key transcription factors and target proteins in renal cell carcinoma and its subtypes.bioRxiv : the preprint server for biology · 2025Article
- Genomic landscape of diffuse glioma revealed by whole genome sequencing.Nature communications · 2025Article
- Chromatin remodeling and cancer: the critical influence of the SWI/SNF complex.Epigenetics & chromatin · 2025Review
- PBRM1 directs PBAF to pericentromeres and protects centromere integrity.Nature communications · 2025Article
- CDC20-Mediated Selective Autophagy Degradation of PBRM1 Affects Immunotherapy for Renal Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Investigating the Role of Osteopontin (OPN) in the Progression of Breast, Prostate, Renal and Skin Cancers.Biomedicines · 2025Article
- The NF-κB signaling network in the life of T cells.Frontiers in immunology · 2025Review
- Chromatin remodeling in lymphocytic function and fate: the multifaceted roles of SWI/SNF complex.Frontiers in immunology · 2025Review
- Alternative splicing of PBRM1 mediates resistance to PD-1 blockade therapy in renal cancer.The EMBO journal · 2024Article
- Chromatin remodellers as therapeutic targets.Nature reviews. Drug discovery · 2024Review
- Preclinical evidence in the assembly of mammalian SWI/SNF complexes: Epigenetic insights and clinical perspectives in human lung disease therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- Targeting SWI/SNF Complexes in Cancer: Pharmacological Approaches and Implications.Epigenomes · 2024Review
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Authors and funding
41 authors at 10 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PBRM1 encodes an accessory subunit of the PBAF SWI/SNF chromatin remodeller, and the inactivation of PBRM1 is a frequent event in kidney cancer. However, the impact of PBRM1 loss on chromatin remodelling is not well examined. Here we show that, in VHL-deficient renal tumours, PBRM1 deficiency results in ectopic PBAF complexes that localize to de novo genomic loci, activating the pro-tumourigenic NF-κB pathway. PBRM1-deficient PBAF complexes retain the association between SMARCA4 and ARID2, but have loosely tethered BRD7. The PBAF complexes redistribute from promoter proximal regions to distal enhancers containing NF-κB motifs, heightening NF-κB activity in PBRM1-deficient models and clinical samples. The ATPase function of SMARCA4 maintains chromatin occupancy of pre-existing and newly acquired RELA specific to PBRM1 loss, activating downstream target gene expression. Proteasome inhibitor bortezomib abrogates RELA occupancy, suppresses NF-κB activation and delays growth of PBRM1-deficient tumours. In conclusion, PBRM1 safeguards the chromatin by repressing aberrant liberation of pro-tumourigenic NF-κB target genes by residual PBRM1-deficient PBAF complexes.
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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.