{"doi":"10.1093/neuonc/noac051","title":"RBBP4-p300 axis modulates expression of genes essential for cell survival and is a potential target for therapy in glioblastoma","abstract":"BACKGROUND: RBBP4 activates transcription by histone acetylation, but the partner histone acetyltransferases are unknown. Thus, we investigated the hypothesis that RBBP4 interacts with p300 in a complex in glioblastoma (GBM). METHODS: shRNA silencing of RBBP4 or p300 and RNAseq was used to identify genes co-regulated by RBBP4 and p300 in GBM43 patient-derived xenograft (PDX). RBBP4/p300 complex was demonstrated using proximity ligation assay (PLA) and ChIPseq delineated histone H3 acetylation and RBBP4/p300 complex binding in promoters/enhancers. Temozolomide (TMZ)-induced DNA double strand breaks (DSBs) were evaluated by γ-H2AX and proliferation by CyQuant and live cell monitoring assays. In vivo efficacy was based on survival of mice with orthotopic tumors. RESULTS: shRBBP4 and shp300 downregulated 4768 genes among which 1485 (31%) were commonly downregulated by both shRNAs, while upregulated genes were 2484, including 863 (35%) common genes. The pro-survival genes were the top-ranked among the downregulated genes, including C-MYC. RBBP4/p300 complex was demonstrated in the nucleus, and shRBBP4 or shp300 significantly sensitized GBM cells to TMZ compared to the control shNT in vitro (P < .05). Moreover, TMZ significantly prolonged the survival of mice bearing GBM22-shRBBP4 orthotopic tumors compared with control shNT tumors (median shNT survival 52 days vs. median shRBBP4 319 days; P = .001). CREB-binding protein (CBP)/p300 inhibitor CPI-1612 suppressed H3K27Ac and RBBP4/p300 complex target proteins, including C-MYC, and synergistically sensitized TMZ in vitro. Pharmacodynamic evaluation confirmed brain penetration by CPI-1612 supporting further investigation to evaluate efficacy to sensitize TMZ. CONCLUSIONS: RBBP4/p300 complex is present in GBM cells and is a potential therapeutic target.","journal":"Neuro-Oncology","year":2022,"id":249742,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":27,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9624,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":323363,"name":"Huihuang Yan","orcid":"0000-0003-0756-2922","position":1,"is_corresponding":false},{"id":451442,"name":"Shulan Tian","orcid":"0000-0002-3348-7439","position":2,"is_corresponding":false},{"id":418165,"name":"Paul A. Decker","orcid":"0000-0002-3756-4227","position":3,"is_corresponding":false},{"id":571256,"name":"Danielle M. Burgenske","orcid":"0000-0003-0014-5579","position":4,"is_corresponding":false},{"id":571258,"name":"Katrina K. Bakken","orcid":"0009-0009-8900-0077","position":5,"is_corresponding":false},{"id":637635,"name":"Zeng Hu","orcid":null,"position":6,"is_corresponding":false},{"id":890572,"name":"Lihong He","orcid":"0000-0002-2694-2974","position":7,"is_corresponding":false},{"id":890573,"name":"Margaret A. Connors","orcid":"0000-0002-0094-0030","position":8,"is_corresponding":false},{"id":463936,"name":"Brett L. Carlson","orcid":"0000-0003-2460-3079","position":9,"is_corresponding":false},{"id":890574,"name":"Jonathan E. Wilson","orcid":"0000-0002-7943-5861","position":10,"is_corresponding":false},{"id":891104,"name":"Archana Bommi‐Reddy","orcid":null,"position":11,"is_corresponding":false},{"id":891105,"name":"Andy Conery","orcid":null,"position":12,"is_corresponding":false},{"id":414223,"name":"Jeanette E. Eckel‐Passow","orcid":"0000-0002-6113-1114","position":13,"is_corresponding":false},{"id":32019,"name":"Jann N. Sarkaria","orcid":"0000-0001-7489-4885","position":14,"is_corresponding":false},{"id":891106,"name":"Gaspar J. Kitange","orcid":null,"position":15,"is_corresponding":false},{"id":571257,"name":"Ann C. Mladek","orcid":"0000-0002-0508-6531","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T00:24:23.754337Z","pmid":"35231103","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}