{"doi":"10.17615/n1jg-tc31","title":"Compensation of BRG-1 Function by Brm: INSIGHT INTO THE ROLE OF THE CORE SWI·SNF SUBUNITS IN RETINOBLASTOMA TUMOR SUPPRESSOR SIGNALING","abstract":"The BRG-1 subunit of the SWI-SNF complex is involved in chromatin remodeling and has been implicated in the action of the retinoblastoma tumor suppressor (RB). Given the importance of BRG-1 in RB function, germ line BRG-1 mutations in tumorigenesis may be tantamount to RB inactivation. Therefore, in this study we assessed the behavior of cells harboring discrete BRG-1 alleles for the RB-signaling pathway. Using p16ink4a, an upstream activator of endogenous RB, or a constitutively active RB construct (PSM-RB), we determined that the majority of tumor lines with germ line defects in BRG-1 were sensitive to RB-mediated cell cycle arrest. By contrast, A427 (lung carcinoma) cells were resistant to expression of p16ink4a and PSM-RB. Analysis of the SWI-SNF subunits in the different tumor lines revealed that A427 are deficient for BRG-1 and its homologue, Brm, whereas RB-sensitive cell lines retained Brm expression. Similarly, the RB-resistant SW13 and C33A cell lines were also deficient for both BRG-1/Brm. Reintroduction of either BRG-1 or Brm into A427 or C33A cells restored RB-mediated signaling to cyclin A to cause cell cycle arrest. Consistent with this compensatory role, we observed that Brm could also drive expression of CD44. We also determined that loss of these core SWI-SNF subunits renders SW13 cells resistant to activation of the RB pathway by the chemotherapeutic agent cisplatin, since reintroduction of either BRG-1 or Brm into SW13 cells restored the cisplatin DNA-damage checkpoint. Together, these data demonstrate that Brm can compensate for BRG-1 loss as pertains to RB sensitivity.","journal":"UNC Libraries","year":2021,"id":210829,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9597,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":65835,"name":"Bernard E. Weissman","orcid":"0000-0002-1827-2309","position":1,"is_corresponding":false},{"id":799739,"name":"David Reisman","orcid":"0000-0002-7028-8500","position":2,"is_corresponding":false},{"id":800326,"name":"Ranjaka W. Gunawardena","orcid":null,"position":3,"is_corresponding":false},{"id":599158,"name":"Matthew W. Strobeck","orcid":null,"position":4,"is_corresponding":false},{"id":391152,"name":"Steven P. Angus","orcid":"0000-0002-7655-657X","position":5,"is_corresponding":false},{"id":796792,"name":"Bryan L. Betz","orcid":null,"position":6,"is_corresponding":false},{"id":260454,"name":"Erik S. Knudsen","orcid":"0000-0002-5130-5969","position":7,"is_corresponding":false},{"id":472909,"name":"Timothy F. Kowalik","orcid":"0000-0001-6096-3018","position":8,"is_corresponding":false},{"id":573713,"name":"Karen E. Knudsen","orcid":"0000-0002-1301-890X","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:52:16.049481Z","pmid":null,"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":[]}