Differential recruitment of nuclear coregulators directs the isoform-dependent action of mutant thyroid hormone receptors.

ABSTRACT: Studies using mice deficient in thyroid hormone receptors (TR) indicate that the two TR isoforms, TRα1 and TRβ1, 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 TRα1 (Thra1(PV) mice) or β1 (Thrb(PV) 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 (NCo

SUBMITTER: Fozzatti L 

PROVIDER: S-EPMC3100599 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature