TY - JOUR
T1 - Thyroid hormone-independent interaction between the thyroid hormone receptor β2 amino terminus and coactivators
AU - Oberste-Berghaus, Corinna
AU - Zanger, Kerstin
AU - Hashimoto, Koshi
AU - Cohen, Ronald N.
AU - Hollenberg, Anthony N.
AU - Wondisford, Fredric E.
PY - 2000/1/21
Y1 - 2000/1/21
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0034695689&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034695689&partnerID=8YFLogxK
U2 - 10.1074/jbc.275.3.1787
DO - 10.1074/jbc.275.3.1787
M3 - Article
C2 - 10636876
AN - SCOPUS:0034695689
SN - 0021-9258
VL - 275
SP - 1787
EP - 1792
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 3
ER -