{"doi":"10.1128/mcb.22.22.7877-7888.2002","title":"The Retinoblastoma Protein Binds the Promoter of the Survival Gene <i>bcl-2</i> and Regulates Its Transcription in Epithelial Cells through Transcription Factor AP-2","abstract":null,"journal":"Molecular and Cellular Biology","year":2002,"id":588816,"datarank":3.9055107385184944,"base_score":4.143134726391533,"endowment":4.143134726391533,"self_citation_contribution":0.62147020895873,"citation_network_contribution":3.2840405295597646,"self_endowment_contribution":0.62147020895873,"citer_contribution":3.2840405295597646,"corpus_percentile":null,"corpus_rank":null,"citation_count":62,"citer_count":61,"citers_with_citation_signal":55,"citers_with_endowment":55,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1506464,"name":"Julien T. Decesse","orcid":null,"position":1,"is_corresponding":false},{"id":68910,"name":"Vasily Ogryzko","orcid":"0000-0002-8548-1389","position":2,"is_corresponding":false},{"id":90289,"name":"John C. Reed","orcid":null,"position":3,"is_corresponding":false},{"id":1506467,"name":"Irina Naguibneva","orcid":null,"position":4,"is_corresponding":false},{"id":1506468,"name":"Annick Harel-Bellan","orcid":null,"position":5,"is_corresponding":false},{"id":1506469,"name":"Chantal E. Cremisi","orcid":null,"position":6,"is_corresponding":false},{"id":1506463,"name":"Stephanie Decary","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The Retinoblastoma Protein Binds the Promoter of the Survival Gene <i>bcl-2</i> and Regulates Its Transcription in Epithelial Cells through Transcription Factor AP-2","abstract":"The retinoblastoma (RB) gene product has been shown to restrict cell proliferation, promote cell differentiation, and inhibit apoptosis. Loss of RB function can induce both p53-dependent apoptosis and p53-independent apoptosis; little is known about the mechanisms of RB-regulated p53-independent apoptosis. Here we show that RB specifically activates transcription of the survival gene bcl-2 in epithelial cells but not in NIH 3T3 mesenchymal cells. This transcriptional activity is mediated by the transcription factor AP-2. By monitoring protein-DNA interactions in living cells using formaldehyde cross-linking and chromatin immunoprecipitation, we show that endogenous RB and AP-2 both bind to the same bcl-2 promoter sequence. In addition, we demonstrate that RB and AP-2 also bind to the E-cadherin gene promoter in vivo, consistent with regulation of this promoter by both AP-2 and RB in epithelial cells. This study provides evidence that RB activates bcl-2 and E-cadherin by binding directly to the respective promoter sequences and not indirectly by repressing an inhibitor. This recruitment is mediated by a transcription factor, in this case AP-2. For the first time, our results suggest a direct molecular mechanism by which RB might inhibit apoptosis independently of p53. The results are discussed in a context where RB and Bcl-2 contribute under nonpathological conditions to the maintenance of cell viability in association with a differentiated phenotype, contributing to the tumor suppressor function of RB and playing important roles in normal development.","is_dataset_classified":null,"base_score":4.143134726391533,"endowment":4.143134726391533,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"12391156","pmcid":"PMC134726","openalex_id":"https://openalex.org/W2131193695","authors":[],"funders":[{"funder_name":"NIGMS NIH HHS","grant_id":"GM-60554","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM060554","title":null}],"total_grants":2,"fwci":2.8445,"citation_percentile":0.9094539,"influential_citations":0,"citation_trend":[{"year":2012,"count":1},{"year":2013,"count":3},{"year":2014,"count":1},{"year":2015,"count":1},{"year":2017,"count":1},{"year":2018,"count":1},{"year":2023,"count":2}],"oa_status":"green","license":"https://journals.asm.org/non-commercial-tdm-license","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/134726","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/134726","host_type":"repository"},{"url":"https://journals.asm.org/doi/pdf/10.1128/MCB.22.22.7877-7888.2002","host_type":"publisher"},{"url":"https://www.tandfonline.com/doi/pdf/10.1128/MCB.22.22.7877-7888.2002","host_type":"publisher"},{"url":"https://doi.org/10.1128/mcb.22.22.7877-7888.2002","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/12391156","host_type":"repository"}],"fields_of_study":["Cancer-related Molecular Pathways","Ubiquitin and proteasome pathways","Retinoids in leukemia and cellular processes"],"mesh_terms":["Acetylation","Cell Line","Chromatin","DNA-Binding Proteins","Epithelial Cells","Gene Expression Regulation","Histones","Humans","Models, Genetic","Promoter Regions, Genetic","Protein Binding","Recombinant Fusion Proteins","Transcription Factors","Transcriptional Activation","Cadherins","Retinoblastoma Protein","Genes, Reporter","Proto-Oncogene Proteins c-bcl-2","Transcription Factor AP-2"],"keywords":["Biology","TCF4","Transcription factor","TAF2","Sp3 transcription factor","Transcription (linguistics)","Molecular biology","Promoter","E-box","DNA-binding protein","Cancer research","Retinoblastoma","Sp1 transcription factor","Response element","General transcription factor","Gene","Cell biology","Genetics","Enhancer","Gene expression"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"gen"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-22T22:09:10.966806Z","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":[]}