Dominant Negative Activity by Estrogen and Progesterone Receptors

摘要: Studies on the autosomal dominant syndrome of thyroid hormone resistance have shown that affected patients a mutant allele for one receptor (TR) isoforms, TRβ (Refetoff et al, 1993). These mutations usually alter codons in carboxy-terminal domain and often result decreased ligand-binding affinity. Additionally, natural receptors are able to block transcriptional activation by both wild-type isoforms (TRα TRβ), thus “dominant negative activity” this TR function. The mechanism activity appears be competition DNA binding TREs between complexes (homo — and/or heterodimers) ligandbound (Figure 1, panel B) (Nagaya 1992; Yen 1992). exclusion transcriptionally active from TRE results blockade T3-stimulated activation.