Isoform-Specific Transcriptional Regulation by Thyroid Hormone Receptors: Hormone-Independent Activation Operates through a Steroid Receptor Mode of Coactivator Interaction | Zendy

Zhihong Yang | Zendy; Martin L. Privalsky | Zendy

Open Access

Isoform-Specific Transcriptional Regulation by Thyroid Hormone Receptors: Hormone-Independent Activation Operates through a Steroid Receptor Mode of Coactivator Interaction

Author(s) -

Zhihong Yang,

Martin L. Privalsky

Publication year - 2001

Publication title -

molecular endocrinology

Language(s) - English

Resource type - Journals

eISSN - 1944-9917

pISSN - 0888-8809

DOI - 10.1210/mend.15.7.0656

Subject(s) - thyroid hormone receptor , biology , thyroid hormone receptor beta , steroid hormone , pelp 1 , nuclear receptor , hormone receptor , hormone , steroid hormone receptor , coactivator , receptor , gene isoform , hormone response element , activator (genetics) , transcription factor , thyrotropin releasing hormone receptor , microbiology and biotechnology , biochemistry , genetics , estrogen receptor , gene , breast cancer , cancer

Thyroid hormone receptors (T3Rs) are hormone-regulated transcription factors that play important roles in vertebrate homeostasis, differentiation, and development. T3Rs are synthesized as multiple isoforms that display tissue-specific expression patterns and distinct transcriptional properties. Most T3R isoforms associate with coactivator proteins and mediate transcriptional activation only in the presence of thyroid hormone. The pituitary-specific T3Rβ-2 isoform departs from this general rule and is able to interact with p160 coactivators, and to mediate transcriptional activation in both the absence and presence of hormone. We report here that this hormone-independent activation is mediated by contacts between the unique N terminus of T3Rβ-2 and an internal interaction domain in the SRC-1 (steroid receptor coactivator-1) and GRIP-1 (glucocorticoid receptor interacting protein 1) coactivators. These hormone-independent contacts between T3Rβ-2 and the p160 coactivators are distinct in sequence and function from the LXXLL motifs that mediate hormone-dependent transcriptional activation and resemble instead a mode of coactivator recruitment previously observed only for the steroid hormone receptors and only in the presence of steroid hormone. Our results suggest that the transcriptional properties of the different T3R isoforms represent a combinatorial mixture of repression, antirepression, and hormone-independent and hormone-dependent activation functions that operate in conjunction to determine the ultimate transcriptional outcome.

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