Studies using @entity19 deficient in @entity6145 receptors (TR) indicate that the two TR isoforms, TRa1 and @entity28659 , in addition to mediating overlapping biological activities of the @entity6145 , T3, also mediate distinct functions. @entity19 harboring an identical dominant negative mutation (denoted PV) at the C terminus of TRa1 (Thra1(PV) @entity19 ) or b1 (Thrb(PV) @entity19 ) also exhibit distinct phenotypes. These knockin mutant @entity19 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 ( @entity39062 ) and six other proteins preferentially associated with TRa1PV or TRb1PV, respectively. These results indicate that recruitment of nuclear regulatory proteins by TR mutants is subtype dependent. The involvement of @entity39062 in mediating the distinct liver phenotype of Thra1(PV) and Thrb(PV) @entity19 was further explored. @entity39062 preferentially interacted with TRa1PV rather than with TRb1PV. @entity39062 was recruited more avidly to the @entity6145 response element-bound TRa1PV than to @entity28659 PV in the promoter of the CCAAT/enhancer-binding protein a gene to repress its expression in the liver of Thra1(PV) @entity19 , but not in Thrb(PV) @entity19 . This preferential recruitment of @entity39062 by mutant isoforms could contribute, at least in part, to the distinct liver lipid phenotype of these mutant @entity19 . The present study highlights a novel mechanism by which TR isoforms direct their selective functions via preferential recruitment of a subset of nuclear coregulatory proteins.

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

@entity19 :: ('10090', 'Species') :: ['mice', 'Mice'] @entity28659 :: ('211770(Tax:10090)', 'Gene') :: ['TRb1'] @entity6145 :: ('CHEBI:60311', 'Chemical') :: ['thyroid hormone'] @entity39062 :: ('20185(Tax:10090)', 'Gene') :: ['NCoR1']
@entity6145 :: (CHEBI:60311,Chemical) :: ['thyroid hormone']
