Thyroid hormones signaling is getting more complex: STORMs are coming.
T3 regulates many physiological and developmental processes by binding to thyroid hormone receptors (TRs). This induces a conformational change of DNA-bound TRs that releases corepressors in favor of coactivators. The associated chromatin modifications induce polymerase II recruitment. Mouse genetic studies clarified the respective contribution of each receptor isoform and revealed the important activity of unliganded TRs. They also confirm the paradoxical negative regulation of some promoters by liganded TRs. Recent advances place these molecular events in a broader context of extra- and intracellular regulation: control of ligand availability, changes in the cell sensitivity to T3, nongenomic effects, and cross talks with other signaling pathways contribute to increase the diversity and complexity of thyroid hormones signaling. A promising novel class of TRs synthetic ligands, called STORMs (selective TR modulators), might allow for tissue- and promoter-specific interventions.
Flamant
Frederic
F
Laboratory of Molecular Cell Biology, Unité Mixte de Recherche, Centre National de la Recherche Scientifique 5161, Institut National de la Recherche Agronomique 1237, France. Frederic.Flamant@ens-lyon.fr
Gauthier
Karine
K
Samarut
Jacques
J
D000818:Animals; D008024:Ligands; D051379:Mice; D020033:Protein Isoforms / Q000378:metabolism; D020239:Receptor Cross-Talk; D011988:Receptors, Thyroid Hormone / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction; D013963:Thyroid Hormones / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
D008024:Ligands; D020033:Protein Isoforms; D011988:Receptors, Thyroid Hormone; D012097:Repressor Proteins; D013963:Thyroid Hormones; D014157:Transcription Factors