{"doi":"10.1073/pnas.191152098","title":"Distinct effects of cAMP and mitogenic signals on CREB-binding protein recruitment impart specificity to target gene activation via CREB","abstract":"<jats:p>Ser-133 phosphorylation of the cAMP-responsive element-binding protein (CREB) is sufficient to induce cellular gene expression in response to cAMP, but additional promoter-bound factors are required for target gene activation by CREB in response to mitogen/stress signals. To compare the relative effects of different signals on recruitment of the coactivator CREB-binding protein (CBP) to CREB in living cells, we developed a fluorescence resonance energy transfer (FRET) assay. cAMP promoted the interaction of CREB with CBP in a phosphorylation-dependent manner by FRET analysis, but mitogen/stress signals were far less effective in stimulating complex formation even though they induced comparable levels of Ser-133 phosphorylation. cAMP and non-cAMP stimuli were comparably active in promoting this interaction in the cytosol; the formation of CREB⋅CBP complexes in response to non-cAMP signals was specifically inhibited in the nucleus. Non-cAMP signals had no effect on intrinsic CREB- or CBP-binding activities by Far Western blot assay, thereby supporting the presence of a distinct CREB⋅CBP antagonist. Our studies indicate that the relative effects of cAMP and mitogen/stress signals on CREB⋅CBP complex formation impart selectivity to gene activation through CREB phosphorylated at Ser-133.</jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2001,"id":607896,"datarank":0.8069846030310691,"base_score":5.37989735354046,"endowment":5.37989735354046,"self_citation_contribution":0.8069846030310691,"citation_network_contribution":0.0,"self_endowment_contribution":0.8069846030310691,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":216,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"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":898316,"name":"Gianluca Canettieri","orcid":"0000-0001-6694-2613","position":1,"is_corresponding":false},{"id":1561023,"name":"Marc R. 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To compare the relative effects of different signals on recruitment of the coactivator CREB-binding protein (CBP) to CREB in living cells, we developed a fluorescence resonance energy transfer (FRET) assay. cAMP promoted the interaction of CREB with CBP in a phosphorylation-dependent manner by FRET analysis, but mitogen/stress signals were far less effective in stimulating complex formation even though they induced comparable levels of Ser-133 phosphorylation. cAMP and non-cAMP stimuli were comparably active in promoting this interaction in the cytosol; the formation of CREB⋅CBP complexes in response to non-cAMP signals was specifically inhibited in the nucleus. Non-cAMP signals had no effect on intrinsic CREB- or CBP-binding activities by Far Western blot assay, thereby supporting the presence of a distinct CREB⋅CBP antagonist. Our studies indicate that the relative effects of cAMP and mitogen/stress signals on CREB⋅CBP complex formation impart selectivity to gene activation through CREB phosphorylated at Ser-133.</jats:p>","is_dataset_classified":null,"base_score":5.37989735354046,"endowment":5.37989735354046,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"11535812","pmcid":"PMC58577","openalex_id":"https://openalex.org/W1997845879","authors":[],"funders":[{"funder_name":"NIGMS NIH HHS","grant_id":"R01-GM37828","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R37 GM037828","title":null}],"total_grants":2,"fwci":4.694,"citation_percentile":0.95671381,"influential_citations":0,"citation_trend":[{"year":2012,"count":6},{"year":2013,"count":12},{"year":2014,"count":7},{"year":2015,"count":5},{"year":2016,"count":7},{"year":2017,"count":8},{"year":2018,"count":3},{"year":2019,"count":5},{"year":2020,"count":3},{"year":2021,"count":20},{"year":2022,"count":19},{"year":2023,"count":1},{"year":2024,"count":1}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/58577","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/58577","host_type":"repository"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.191152098","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.191152098","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/11535812","host_type":"repository"},{"url":"http://hdl.handle.net/11573/143214","host_type":"repository"}],"fields_of_study":["Receptor Mechanisms and Signaling","Viral Infectious Diseases and Gene Expression in Insects","CRISPR and Genetic Engineering"],"mesh_terms":["Cyclic AMP","Animals","Cell Line","Gene Expression Regulation","Humans","Mitogens","Nuclear Proteins","Phosphorylation","Serine","Tetradecanoylphorbol Acetate","Signal Transduction","Transcriptional Activation","Trans-Activators","PC12 Cells","Cyclic AMP Response Element-Binding Protein","CREB-Binding Protein","Rats"],"keywords":["CREB","CREB-binding protein","Phosphorylation","Cyclic AMP Response Element-Binding Protein","CREB1","Coactivator","Cell biology","Biology","Molecular biology","Chemistry","Gene","Transcription factor","Biochemistry"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Affordable and clean energy"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-30T07:11:32.889271Z","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":[]}