T. Monden et al., ISOLATION AND CHARACTERIZATION OF A NOVEL LIGAND-DEPENDENT THYROID-HORMONE RECEPTOR-COACTIVATING PROTEIN, The Journal of biological chemistry, 272(47), 1997, pp. 29834-29841
The thyroid hormone receptor (TR) regulates the expression of target g
enes upon binding to triiodothyro nine (T-3) response elements, In the
presence of T-3, the TR recruits coactivating proteins that both modu
late and integrate the ligand response, We report here the cloning of
a novel protein using the TR ligand-binding domain as bait in the yeas
t two-hybrid system. Analysis of a putative full length clone demonstr
ates a cDNA sequence that encodes a protein of 920 amino acids with a
size of 120 kDa (p120), Alignment with known sequences shows homology
to a previously identified protein of unknown function, termed skeleta
l muscle abundant protein, Interaction studies demonstrate that p120 i
nteracts with the TR AF-2 domain in the presence of ligand through a 1
11-amino acid region. Northern analysis demonstrates widespread expres
sion in human tissues. Cotransfection assays in CV-1 cells demonstrate
that p120 enhances TR-mediated transactivation on multiple T-3 respon
se elements in the presence of T-3. In addition, CREB-binding protein
synergizes with p120 to enhance this effect. When linked to the GAL4 D
NA-bind ing domain, p120 is an activator of transcription alone. Thus,
p120 satisfies a number of important criteria as a nuclear receptor c
oactivator.