{"id":{"repo_id":"utmb","oai_identifier":"oai:utmb-ir.tdl.org:2152.3/12324"},"canonical_url":"https://search.dev.ndltd.org/etd/utmb/oai:utmb-ir.tdl.org:2152.3/12324","repository":{"repo_id":"utmb","name":"University of Texas Medical Branch","base_url":"https://utmb-ir.tdl.org/server/oai/request"},"display":{"title":"Investigation of ARNT isoform-specific regulation of AHR signaling","abstract":"The aryl hydrocarbon receptor nuclear translocator (ARNT) is alternatively spliced into two distinct isoforms, isoform 1 and 3. Although ARNT is found to be critical in immunity, xenobiotic, and hypoxic response, ARNT isoform-specific function has yet to be investigated. We previously demonstrated that primary lymphocytes express both of these isoforms, however malignant T cells overexpress ARNT isoform 1 to promote cell viability. In this study, we find that the ARNT isoforms have opposing roles in aryl hydrocarbon receptor (AHR) signaling, as ARNT isoform 1 suppresses AHR activity, whereas ARNT isoform 3 is needed for AHR target-gene transcription. Furthermore, to explore this suppressive role, we investigated a unique modification specific only to ARNT isoform 1 – phosphorylation of serine 77 (S77). We determined that phosphorylation at S77 is initiated following AHR activation and is critical for the augmentation of AHR-target gene transcription. These results further highlight the importance of investigating ARNT isoform-specific function and reveal an essential role of ARNT isoform 1 phosphorylation in AHR signaling. Collectively, these findings increase our understanding of a complex regulatory mechanism by which ARNT regulates AHR signaling, further aiding in the comprehension of their roles in immunity and supporting the potential of targeting ARNT alternative splicing as a means of therapeutic intervention in hematological diseases and malignancies.","abstract_html":"The aryl hydrocarbon receptor nuclear translocator (ARNT) is alternatively spliced into two distinct isoforms, isoform 1 and 3. Although ARNT is found to be critical in immunity, xenobiotic, and hypoxic response, ARNT isoform-specific function has yet to be investigated. We previously demonstrated that primary lymphocytes express both of these isoforms, however malignant T cells overexpress ARNT isoform 1 to promote cell viability. In this study, we find that the ARNT isoforms have opposing roles in aryl hydrocarbon receptor (AHR) signaling, as ARNT isoform 1 suppresses AHR activity, whereas ARNT isoform 3 is needed for AHR target-gene transcription. Furthermore, to explore this suppressive role, we investigated a unique modification specific only to ARNT isoform 1 – phosphorylation of serine 77 (S77). We determined that phosphorylation at S77 is initiated following AHR activation and is critical for the augmentation of AHR-target gene transcription. These results further highlight the importance of investigating ARNT isoform-specific function and reveal an essential role of ARNT isoform 1 phosphorylation in AHR signaling. Collectively, these findings increase our understanding of a complex regulatory mechanism by which ARNT regulates AHR signaling, further aiding in the comprehension of their roles in immunity and supporting the potential of targeting ARNT alternative splicing as a means of therapeutic intervention in hematological diseases and malignancies.","abstract_has_math":false,"creators":["Bourner, Luke"],"institution":"The University of Texas Medical Branch at Galveston","degree_name":"Pharmacology and Toxicology (Doctoral)","degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2021,"date_issued":"May 2021","date_published":"May 2021","updated_at":"2026-07-24T05:50:48Z","subjects":["Health Sciences, Toxicology","Biology, Molecular"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2152.3/12324","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Bourner, Luke"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2024-03-11T21:34:53Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2024-03-11T21:34:53Z"]},{"key":"dc:date.issued","label":"Date","values":["May 2021"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Pharmacology and Toxicology (Doctoral)"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["The University of Texas Medical Branch at Galveston"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Health Sciences, Toxicology","Biology, Molecular"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/2152.3/12324"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The aryl hydrocarbon receptor nuclear translocator (ARNT) is alternatively spliced into two distinct isoforms, isoform 1 and 3. Although ARNT is found to be critical in immunity, xenobiotic, and hypoxic response, ARNT isoform-specific function has yet to be investigated. We previously demonstrated that primary lymphocytes express both of these isoforms, however malignant T cells overexpress ARNT isoform 1 to promote cell viability. In this study, we find that the ARNT isoforms have opposing roles in aryl hydrocarbon receptor (AHR) signaling, as ARNT isoform 1 suppresses AHR activity, whereas ARNT isoform 3 is needed for AHR target-gene transcription. Furthermore, to explore this suppressive role, we investigated a unique modification specific only to ARNT isoform 1 – phosphorylation of serine 77 (S77). We determined that phosphorylation at S77 is initiated following AHR activation and is critical for the augmentation of AHR-target gene transcription. These results further highlight the importance of investigating ARNT isoform-specific function and reveal an essential role of ARNT isoform 1 phosphorylation in AHR signaling. Collectively, these findings increase our understanding of a complex regulatory mechanism by which ARNT regulates AHR signaling, further aiding in the comprehension of their roles in immunity and supporting the potential of targeting ARNT alternative splicing as a means of therapeutic intervention in hematological diseases and malignancies."]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Investigation of ARNT isoform-specific regulation of AHR signaling"]}]}],"canonical_facts":{"dc:creator":["Bourner, Luke"],"dc:date.accessioned":["2024-03-11T21:34:53Z"],"dc:date.available":["2024-03-11T21:34:53Z"],"dc:date.issued":["May 2021"],"dc:description.abstract":["The aryl hydrocarbon receptor nuclear translocator (ARNT) is alternatively spliced into two distinct isoforms, isoform 1 and 3. Although ARNT is found to be critical in immunity, xenobiotic, and hypoxic response, ARNT isoform-specific function has yet to be investigated. We previously demonstrated that primary lymphocytes express both of these isoforms, however malignant T cells overexpress ARNT isoform 1 to promote cell viability. In this study, we find that the ARNT isoforms have opposing roles in aryl hydrocarbon receptor (AHR) signaling, as ARNT isoform 1 suppresses AHR activity, whereas ARNT isoform 3 is needed for AHR target-gene transcription. Furthermore, to explore this suppressive role, we investigated a unique modification specific only to ARNT isoform 1 – phosphorylation of serine 77 (S77). We determined that phosphorylation at S77 is initiated following AHR activation and is critical for the augmentation of AHR-target gene transcription. These results further highlight the importance of investigating ARNT isoform-specific function and reveal an essential role of ARNT isoform 1 phosphorylation in AHR signaling. Collectively, these findings increase our understanding of a complex regulatory mechanism by which ARNT regulates AHR signaling, further aiding in the comprehension of their roles in immunity and supporting the potential of targeting ARNT alternative splicing as a means of therapeutic intervention in hematological diseases and malignancies."],"dc:format.mimetype":["application/pdf"],"dc:identifier.uri":["https://hdl.handle.net/2152.3/12324"],"dc:subject":["Health Sciences, Toxicology","Biology, Molecular"],"dc:title":["Investigation of ARNT isoform-specific regulation of AHR signaling"],"dc:type":["Thesis"],"thesis:degree_name":["Pharmacology and Toxicology (Doctoral)"],"thesis:institution_name":["The University of Texas Medical Branch at Galveston"]},"updated_at":"2026-07-24T05:50:48Z"}