Differential Recruitment of Nuclear Coregulators Directs the Isoform-Dependent Action of Mutant Thyroid Hormone Receptors

LAURA FOZZATTI; LU CHANGXUE; KIM DONG-WOOK; CHENG SHEUE-YANN

ENDOCRINE SOC

Año: 2011 p. 908 - 908

Studies using mice deficient in thyroid hormone receptors (TR) indicate that the two TR isoforms, TR1 and TR1, in addition to mediating overlapping biological activities of the thyroid hormone, T3, also mediate distinct functions. Mice harboring an identical dominant negative mutation (denoted PV) at the C terminus of TR1 (Thra1PV mice) or 1 (ThrbPV mice) also exhibit distinct phenotypes. These knockin mutant mice provide an opportunity to understand the molecular basis of isoform-dependent functions in vivo. Here we tested the hypothesis that the distinct functions of TR mutant isoforms are directed by a subset of nuclear regulatory proteins. Tandem-affinity chromatography of HeLa nuclear extracts showed that distinct 33 nuclear proteins including nuclear receptor corepressor (NCoR1) and six other proteins preferentially associated with TR1PV or TR1PV, respectively. These results indicate that recruitment of nuclear regulatory proteins by TR mutants is subtype dependent. The inv