Thyroid hormone-independent interaction between the thyroid hormone receptor β2 amino terminus and coactivators

Corinna Oberste-Berghaus, Kerstin Zanger, Koshi Hashimoto, Ronald N. Cohen, Anthony N. Hollenberg, Fredric E. Wondisford

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

Thyroid hormone receptors (TRs) mediate hormone action by binding to DNA response elements (TREs) and either activating or repressing gene expression in the presence of ligand, T3. Coactivator recruitment to the AF-2 region of TR in the presence of T3 is central to this process. The different TR isoforms, TR-β1, TR-β2, and TR-α1, share strong homology in their DNA- and ligandbinding domains but differ in their amino-terminal domains. Because TR- β2 exhibits greater T3-independent activation on TREs than other TR isoforms, we wanted to determine whether coactivators bound to TR-β2 in the absence of ligand. Our results show that TR-β2, unlike TR-β1 or TR-α1, is able to bind certain coactivators (CBP, SRC-1, and pCIP) in the absence of T3 through a domain which maps to the amino-terminal half of its A/B domain. This interaction is specific for certain coactivators, as TR-β2 does not interact with other co-factors (p120 or the CBP-associated factor (pCAF)) in the absence of T3. The minimal TR-β2 domain for coactivator binding is aa 21-50, although aa 1-50 are required for the full functional response. Thus, isoform-specific regulation by TRs may involve T3-independent coactivator recruitment to the transcription complex via the AF-1 domain.

Original languageEnglish (US)
Pages (from-to)1787-1792
Number of pages6
JournalJournal of Biological Chemistry
Volume275
Issue number3
DOIs
StatePublished - Jan 21 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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