dc.contributor.author | Arseven, OK | |
dc.contributor.author | Jameson, JL | |
dc.contributor.author | Tagami, T | |
dc.contributor.author | Kopp, P | |
dc.contributor.author | Johnson, W | |
dc.date.accessioned | 2022-02-18T11:13:42Z | |
dc.date.available | 2022-02-18T11:13:42Z | |
dc.date.issued | 1998 | |
dc.identifier.citation | Tagami T., Kopp P., Johnson W., Arseven O., Jameson J., "The thyroid hormone receptor variant alpha 2 is a weak antagonist because it is deficient in interactions with nuclear receptor corepressors", ENDOCRINOLOGY, cilt.139, sa.5, ss.2535-2544, 1998 | |
dc.identifier.issn | 0013-7227 | |
dc.identifier.other | vv_1032021 | |
dc.identifier.other | av_e0021c10-a4ea-4281-bfe9-a3f9142adcbe | |
dc.identifier.uri | http://hdl.handle.net/20.500.12627/180704 | |
dc.identifier.uri | https://doi.org/10.1210/en.139.5.2535 | |
dc.description.abstract | The thyroid hormone receptor splice variant, alpha 2, is unable to bind thyroid hormone (T-3) and has been proposed to function as an endogenous inhibitor of T-3 action. In this report, we examined further the DNA sequence requirements for alpha 2 binding to thyroid hormone response elements (TREs) in an attempt to identify response elements that mediate potent inhibition by alpha 2. Heterodimers of alpha 2 and retinoid X receptor were found to bind to a subset of TREs (DR4, direct repeats spaced by 4 bp) in which selected flanking and spacer sequences enhanced interactions with the AGGTCA core binding sequence. Despite the optimization of the TRE-binding sites, alpha 2 remained a weak dominant negative inhibitor of TRE-driven transcription. A promoter interference assay was also developed for testing inhibition by alpha 2. In these studies, alpha 2 blocked gene transcription, but it required cotransfected retinoid X receptor, and it was not as potent as unliganded thyroid hormone receptors. These results led to the hypothesis that alpha 2 might be deficient in interactions with nuclear receptor corepressors. Consistent with this view, alpha 2 did not silence basal transcription in its native form or when linked to Gal4. alpha 2 also failed to interact with corepressors (NCoR and SMRT) in both gel shift assays and mammalian two-hybrid assays. We conclude that alpha 2 is a weak antagonist of thyroid hormone action because it binds weakly to a limited repertoire of response elements, and it does not interact with corepressors. Thus, alpha 2 may be able to compete with thyroid hormone receptors for binding to a limited group of target sites, but it is not able to actively inhibit transcription. | |
dc.language.iso | eng | |
dc.subject | Endocrinology | |
dc.subject | Endocrine and Autonomic Systems | |
dc.subject | Endocrinology, Diabetes and Metabolism | |
dc.subject | Life Sciences | |
dc.subject | Health Sciences | |
dc.subject | İç Hastalıkları | |
dc.subject | Endokrinoloji ve Metabolizma Hastalıkları | |
dc.subject | Dahili Tıp Bilimleri | |
dc.subject | Sağlık Bilimleri | |
dc.subject | Tıp | |
dc.subject | Klinik Tıp (MED) | |
dc.subject | Klinik Tıp | |
dc.subject | ENDOKRİNOLOJİ VE METABOLİZMA | |
dc.title | The thyroid hormone receptor variant alpha 2 is a weak antagonist because it is deficient in interactions with nuclear receptor corepressors | |
dc.type | Makale | |
dc.relation.journal | ENDOCRINOLOGY | |
dc.contributor.department | , , | |
dc.identifier.volume | 139 | |
dc.identifier.issue | 5 | |
dc.identifier.startpage | 2535 | |
dc.identifier.endpage | 2544 | |
dc.contributor.firstauthorID | 3371496 | |