{"doi":"10.1534/genetics.116.198788","title":"The Oxidative Stress Response in <i>Caenorhabditis elegans</i> Requires the GATA Transcription Factor ELT-3 and SKN-1/Nrf2","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>Cellular damage caused by reactive oxygen species is believed to be a major contributor to age-associated diseases. Previously, we characterized the Caenorhabditis elegans Brap2 ortholog (BRAP-2) and found that it is required to prevent larval arrest in response to elevated levels of oxidative stress. Here, we report that C. elegans brap-2 mutants display increased expression of SKN-1-dependent, phase II detoxification enzymes that is dependent on PMK-1 (a p38 MAPK C. elegans ortholog). An RNA-interference screen was conducted using a transcription factor library to identify genes required for increased expression of the SKN-1 target gst-4 in brap-2 mutants. We identified ELT-3, a member of the GATA transcription factor family, as a positive regulator of gst-4p::gfp expression. We found that ELT-3 interacts with SKN-1 to activate gst-4 transcription in vitro and that elt-3 is required for enhanced gst-4 expression in the brap-2(ok1492) mutant in vivo. Furthermore, nematodes overexpressing SKN-1 required ELT-3 for life-span extension. Taken together, these results suggest a model where BRAP-2 acts as negative regulator of SKN-1 through inhibition of p38 MAPK activity, and that the GATA transcription factor ELT-3 is required along with SKN-1 for the phase II detoxification response in C. elegans.</jats:p>","journal":"Genetics","year":2017,"id":621106,"datarank":0.6064576901751826,"base_score":4.04305126783455,"endowment":4.04305126783455,"self_citation_contribution":0.6064576901751826,"citation_network_contribution":0.0,"self_endowment_contribution":0.6064576901751826,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":56,"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":1603624,"name":"Dayana R D’Amora","orcid":null,"position":1,"is_corresponding":false},{"id":1603625,"name":"Lesley T MacNeil","orcid":null,"position":2,"is_corresponding":false},{"id":1603626,"name":"Albertha J M Walhout","orcid":null,"position":3,"is_corresponding":false},{"id":1603627,"name":"Terrance J Kubiseski","orcid":null,"position":4,"is_corresponding":false},{"id":533304,"name":"Queenie Hu","orcid":"0000-0003-4272-5053","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The Oxidative Stress Response in <i>Caenorhabditis elegans</i> Requires the GATA Transcription Factor ELT-3 and SKN-1/Nrf2","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>Cellular damage caused by reactive oxygen species is believed to be a major contributor to age-associated diseases. Previously, we characterized the Caenorhabditis elegans Brap2 ortholog (BRAP-2) and found that it is required to prevent larval arrest in response to elevated levels of oxidative stress. Here, we report that C. elegans brap-2 mutants display increased expression of SKN-1-dependent, phase II detoxification enzymes that is dependent on PMK-1 (a p38 MAPK C. elegans ortholog). An RNA-interference screen was conducted using a transcription factor library to identify genes required for increased expression of the SKN-1 target gst-4 in brap-2 mutants. We identified ELT-3, a member of the GATA transcription factor family, as a positive regulator of gst-4p::gfp expression. We found that ELT-3 interacts with SKN-1 to activate gst-4 transcription in vitro and that elt-3 is required for enhanced gst-4 expression in the brap-2(ok1492) mutant in vivo. Furthermore, nematodes overexpressing SKN-1 required ELT-3 for life-span extension. Taken together, these results suggest a model where BRAP-2 acts as negative regulator of SKN-1 through inhibition of p38 MAPK activity, and that the GATA transcription factor ELT-3 is required along with SKN-1 for the phase II detoxification response in C. elegans.</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"28600327","pmcid":"PMC5560797","openalex_id":null,"authors":[],"funders":[{"funder_name":"NIDDK NIH HHS","grant_id":"R56 DK068429","title":null},{"funder_name":"NIH HHS","grant_id":"P40 OD010440","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK068429","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM082971","title":null}],"total_grants":4,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"bronze","license":"https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model","oa_locations":[{"url":"https://www.genetics.org/content/genetics/206/4/1909.full.pdf","host_type":"publisher"},{"url":"https://academic.oup.com/genetics/article-pdf/206/4/1909/46777507/genetics1909.pdf","host_type":"publisher"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5560797","host_type":"repository"}],"fields_of_study":["Animals","Caenorhabditis elegans","Caenorhabditis elegans Proteins","DNA-Binding Proteins","GATA Transcription Factors","Glutathione Transferase","Mitogen-Activated Protein Kinases","Oxidative Stress","Protein Binding","Transcription Factors"],"mesh_terms":["Animals","Caenorhabditis elegans","Glutathione Transferase","Mitogen-Activated Protein Kinases","DNA-Binding Proteins","Caenorhabditis elegans Proteins","Transcription Factors","Protein Binding","Oxidative Stress","GATA Transcription Factors"],"keywords":["Oxidative stress","Skn-1","Gata Transcription Factors","Elt-3","Brap-2"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T13:14:55.667031Z","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":[]}