Steroid receptors mediate their effects on gene transcription. by interacting with cis-acting enhancer regions known as response elements (REs). Recent evidence from the long terminal repeat of the Mouse Mammary Tumour Virus (MMTV) suggests that glucocorticoid response elements (GREs) may consist of directly-repeated half-sites separated by nine base pairs (GRE-D9). Evidence is provided that GRE-D9 can bind to GR homodimers in vitro, and that, when present in multiple copies, can mediate transactivation of a reporter gene in vivo. / Heat shock protein 90 (hsp90) has been implicated in modulating the ligand-inducibility of the estrogen receptor (ER) in vivo. In order to better characterize the functional significance of the interaction between these two proteins, chimeric ERs consisting of the GAL-4 DNA binding domain fused to the ligand binding domain (LBD) of the ER were constructed. Although these chimeras are ligand-dependent transactivators, they bind DNA in the absence of estradiol and do not interact with hsp90 in vitro. Furthermore, data are presented which are consistent with a model in which transcriptional interact with the ER LBD in a ligand-dependent manner. Introduction of the destabilizing Gly400Val substitution in the ER L33D results in a chimera which is ligand-dependent for both DNA binding and transactivation. These partially destabilized chimeras are shown to interact with hsp90 in vitro in a ligand-dependent manner, whereas chimeras derived from wild-type ER show only a transient association with hsp90, suggesting that hsp90 serves as a molecular chaperone for the ER. A functional model for ER/hsp90 interaction is discussed.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.20799 |
| Date | January 1997 |
| Creators | Aumais, Jonathan Paul. |
| Contributors | White, John H. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Physiology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001604936, proquestno: MQ44120, Theses scanned by UMI/ProQuest. |
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