Thyroid Hormone Receptor Mutations in Cancer and Resistance to Thyroid Hormone: Perspective and Prognosis
Figure 3
Transcriptional activity of wild-type and dominant-negative TRs. (a) In the absence of T3, wild-type TR (orange sphere plus a grey homo- or heterodimer partner) binds to thyroid hormone response elements (TREs-, shown as pink rectangle on DNA), recruits a cohort of corepressor proteins (shown as a red rectangle), and represses transcription of a given target gene (blue rectangle). (b) In the presence of T3 (dark blue sphere), wild-type TRs undergo a conformational change and exchange corepressor proteins for coactivators (green oval) to activate transcription of a target gene. (c) Dominant-negative TR mutants (shown here as a disfigured lavender sphere) have defects in hormone binding, corepressor release, or coactivator recruitment and consequently repress transcription even in the presence of hormone and other wild-type TRs.
