Mutations of CpG dinucleotides located in the triiodothyronine (T3)-binding domain of the thyroid hormone receptor (TR) beta gene that appears to be devoid of natural mutations may not be detected because they are unlikely to produce the clinical phenotype of resistance to thyroid hormone.

A potential role of activated NF-κB in the pathogenesis of euthyroid sick syndrome

“…The constructions of plasmids expressing TRβ, p50 subunit of NF-κB, p65 subunit of NF-κB, a dominant-negative form of p65 (p65 DN), and CREB (c-AMP responsive element binding protein) binding protein (CBP), and the luciferase reporter genes (3xPal TK Luc, TSH-α Luc, and NF-κB pGL3pro Luc) were described previously (22)(23)(24)(25)(26)(27). For the yeast twohybrid system, cDNAs for full-length human TRβ or IκBβ were subcloned into the vector expressing Gal4 DNA-binding domain (DBD) (pGBT9) in-frame.…”

Syndromes of Reduced Sensitivity to Thyroid Hormone

“…Mut TRs interfere with WT TR function by occupying TREs on target genes and by engaging WT TRβ in homodimerization. This explains why no mutations have been identified in CpGs located in regions of the TRβ molecule involved in homodimerization [50]. Dominant negative effect can also manifest through altered association of a mut TRβ with a cofactor, including increased affinity to or decreased release of a corepressor [42,51], or reduced association with a coactivator [40].…”

Unliganded thyroid hormone receptor β1 inhibits proliferation of murine fibroblasts by delaying the onset of the G1 cell-cycle signals

“…The TRb1 point-mutant G345R, which is unable to bind T 3 , is as good repressor as wild-type TRb1. Moreover, transfections with the TRb1 mutants AHT and R429Q (Hayashi et al, 1994;Yen et al, 1995;Baumann et al, 2001) also indicate that functional interaction with the nuclear corepressor NCoR and homodimerization are not required. Only a functional DNA-binding domain appeared to be essential for the action of the TRb1 receptor on E2F-1 activation.…”

“…For transfection experiments mouse NIH-3T3 fibroblasts were used and maintained as above at 5% CO 2 . Reporter plasmids containing three copies of the E2F-1-response element (wild-type or point mutated inactive) from the dihydrofolate-reductase gene driving the transcription of the luciferase gene (Campanero et al, 2000) were used along with vectors either empty (Clontech, Palo Alto, CA, USA) or containing TRa, wild-type TRb or several TRb point mutants (Hayashi et al, 1994;Yen et al, 1995;Baumann et al, 2001). All transfections included 0.5 mg of pCMV-b-galactosidase (Clontech) to test transfection efficiency.…”