Investigation of ARNT isoform-specific regulation of AHR signaling
| dc.creator | Bourner, Luke | |
| dc.date.accessioned | 2024-03-11T21:34:53Z | |
| dc.date.available | 2024-03-11T21:34:53Z | |
| dc.date.created | 2021-05 | |
| dc.date.issued | May 2021 | |
| dc.date.submitted | May 2021 | |
| dc.date.updated | 2024-03-11T21:34:54Z | |
| 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 | ||
| dc.identifier.uri | https://hdl.handle.net/2152.3/12324 | |
| dc.subject | Health Sciences, Toxicology | |
| dc.subject | Biology, Molecular | |
| dc.subject.other | AHR, ARNT, Toxicology, Immunotoxicology | |
| dc.title | Investigation of ARNT isoform-specific regulation of AHR signaling | |
| dc.type | Thesis | |
| dc.type.material | text | |
| local.embargo.lift | 05/01/2024 | |
| local.embargo.terms | 05/01/2024 | |
| thesis.degree.department | Pharmacology and Toxicology | |
| thesis.degree.grantor | The University of Texas Medical Branch at Galveston | |
| thesis.degree.name | Pharmacology and Toxicology (Doctoral) |