| Transcriptional Activation by Steroid/Thyroid Hormone Receptors
Bruce M. Raaka Ph.D.
Departments of Medicine (Endocrinology) and Pharmacology |
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| Research Summary |
| Members of the steroid/thyroid hormone retinoid receptor superfamily are ligand-dependent transcription factors. They interact with DNA through a characteristic domain that consists of two fingers formed by the coordination cysteine residues with two zinc atoms. The ligand binding domains of these receptors are located in their carboxy-terminal regions. These receptors bind as homo- or heterodimers to DNA response elements consisting of direct or inverted repeats of a six base pair consensus sequence that differs for different receptor subgroups. Functional domains for dimerization and for transcriptional activation have also been identified. One of our interests has been to understand the functional role of ligands for these receptors. In early studies, we showed that glucocorticoid agonists bind to and promote dissociation of an oligomeric glucocorticoid receptor that does not bind DNA to a monomeric DNA-binding form. The oligomer was later shown to be a complex between the glucocorticoid receptor and the 90 kDa heat shock protein hsp90. While thyroid hormone receptors do not interact with hsp90, recent studies suggest that binding of thyroid hormone activates its receptor by promoting dissociation of an inhibitory factor. We are working to identify and clone this inhibitory factor and other proteins that interact functionally with thyroid receptors. Another interest is the inhibition of breast tumor cell growth by retinoids. Using a PCR-assisted subtractive hybridization method, we have recently shown that retinoids increase expression of SOX9, a member of a family of transcription factors that has not been previously identified in breast cancer cells. The functional importance of SOX9 and other promising candidate genes in the inhibition of breast tumor cell growth will be evaluated in future studies.
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| Related Images |
Image 1 | Binding of thyroid hormone (T3) promotes dissociation of an inhibitory factor from the ligand binding domain of the chicken thyroid hormone receptor (cT3R). | | |
| Research Information |
Research Interests | Transcriptional Activation by Steroid/Thyroid Hormone Receptors | Research Keywords | glucocorticoid, hormones, receptors, thyroid, transcription |
