TRAM-1, A novel 160-kDa thyroid hormone receptor activator molecule, exhibits distinct properties from steroid receptor coactivator-1
- PMID: 9346901
- DOI: 10.1074/jbc.272.44.27629
TRAM-1, A novel 160-kDa thyroid hormone receptor activator molecule, exhibits distinct properties from steroid receptor coactivator-1
Abstract
Nuclear hormone receptors (NRs) are ligand-dependent transcription factors that regulate target gene transcription. We report the molecular cloning and characterization of a novel human cDNA encoding TRAM-1, a thyroid hormone receptor activator molecule, a approximately 160-kDa protein homologous with SRC-1/TIF2, by far-Western-based expression screening. TRAM-1 binds to thyroid hormone receptor (TR) and other NRs in a ligand-dependent manner and enhances ligand-induced transcriptional activity of TR. The AF-2 region in NRs has been thought to play a critical role in mediating ligand-dependent transactivation by the interaction with coactivators. Surprisingly, TRAM-1 retains strong ligand-dependent interaction with an AF-2 mutant of TR (E457A), while SRC-1 fails to interact with this mutant. Furthermore, we identified a critical TRAM-1 binding site in rat TRbeta1 outside of AF-2, as TRAM-1 shows weak ligand-dependent interaction with a helix 3 ligand binding domain TR mutant (K288A), compared with SRC-1. These results suggest that TRAM-1 is a coactivator that may exhibit its activity by interacting with subdomains of NRs other than the AF-2 region, in contrast to SRC-1/TIF2.
Similar articles
-
Analysis of the functional role of steroid receptor coactivator-1 in ligand-induced transactivation by thyroid hormone receptor.Mol Endocrinol. 1997 Jun;11(6):755-67. doi: 10.1210/mend.11.6.0003. Mol Endocrinol. 1997. PMID: 9171239
-
Molecular cloning and properties of a full-length putative thyroid hormone receptor coactivator.Endocrinology. 1996 Aug;137(8):3594-7. doi: 10.1210/endo.137.8.8754792. Endocrinology. 1996. PMID: 8754792
-
In vivo interaction of steroid receptor coactivator (SRC)-1 and the activation function-2 domain of the thyroid hormone receptor (TR) beta in TRbeta E457A knock-in and SRC-1 knockout mice.Endocrinology. 2009 Aug;150(8):3927-34. doi: 10.1210/en.2009-0093. Epub 2009 Apr 30. Endocrinology. 2009. PMID: 19406944 Free PMC article.
-
Role of co-activators and co-repressors in the mechanism of steroid/thyroid receptor action.Recent Prog Horm Res. 1997;52:141-64; discussion 164-5. Recent Prog Horm Res. 1997. PMID: 9238851 Review.
-
The SRC family of nuclear receptor coactivators.Gene. 2000 Mar 7;245(1):1-11. doi: 10.1016/s0378-1119(00)00024-x. Gene. 2000. PMID: 10713439 Review.
Cited by
-
Acetylation of histones and transcription-related factors.Microbiol Mol Biol Rev. 2000 Jun;64(2):435-59. doi: 10.1128/MMBR.64.2.435-459.2000. Microbiol Mol Biol Rev. 2000. PMID: 10839822 Free PMC article. Review.
-
A histone methyltransferase is required for maximal response to female sex hormones.Mol Cell Biol. 2004 Aug;24(16):7032-42. doi: 10.1128/MCB.24.16.7032-7042.2004. Mol Cell Biol. 2004. PMID: 15282304 Free PMC article.
-
The ubiquitin ligase CHIP acts as an upstream regulator of oncogenic pathways.Nat Cell Biol. 2009 Mar;11(3):312-9. doi: 10.1038/ncb1839. Epub 2009 Feb 8. Nat Cell Biol. 2009. PMID: 19198599
-
Inactivation of the nuclear receptor coactivator RAP250 in mice results in placental vascular dysfunction.Mol Cell Biol. 2003 Feb;23(4):1260-8. doi: 10.1128/MCB.23.4.1260-1268.2003. Mol Cell Biol. 2003. PMID: 12556486 Free PMC article.
-
Quantification of ligand-regulated nuclear receptor corepressor and coactivator binding, key interactions determining ligand potency and efficacy for the thyroid hormone receptor.Biochemistry. 2008 Jul 15;47(28):7465-76. doi: 10.1021/bi800393u. Epub 2008 Jun 18. Biochemistry. 2008. PMID: 18558711 Free PMC article.
MeSH terms
Substances
Associated data
- Actions
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous
