Abstract
Nuclear hormone receptors are transcription factors that require multiple protein-protein interactions to regulate the expression of their target genes. Using the yeast two-hybrid system, we identified a protein, thyroid hormone receptor uncoupling protein (TRUP), that specifically interacts with a region of the human thyroid hormone receptor (TR) consisting of the hinge region and the N-terminal portion of the ligand binding domain in a hormone-independent manner. Interestingly, TRUP inhibits transactivation by TR and the retinoic acid receptor but has no effect on the estrogen receptor or the retinoid X receptor in mammalian cells. We also demonstrate that TRUP exerts its action on TR and retinoic acid receptor by interfering with their abilities to interact with their DNA. TRUP represents a type of regulatory protein that modulates the transcriptional activity of a subclass of the nuclear hormone receptor superfamily by preventing interaction with their genomic response elements.
MeSH Terms
Amino Acid Sequence
Animals
Humans
Molecular Sequence Data
Protein Binding
Receptors, Estrogen/metabolism
Receptors, Retinoic Acid/metabolism
Receptors, Thyroid Hormone/metabolism
Repressor Proteins/genetics,metabolism
Retinoid X Receptors
Ribosomal Proteins/genetics,metabolism
Transcription Factors/metabolism
Transcriptional Activation
Chemicals
RPL7A protein, human
Receptors, Estrogen
Receptors, Retinoic Acid
Receptors, Thyroid Hormone
Repressor Proteins
Retinoid X Receptors
Ribosomal Proteins
Transcription Factors
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Burris T P
Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Nawaz Z
Tsai M J
O'Malley B W
References (27)
27 references, click to expand
-
Ribosomal protein L7a is encoded by a gene (Surf-3) within the tightly clustered mouse surfeit locus.
Mol Cell Biol. 1989 Jan;9(1):224-31
PMID: 2648130
-
Transcription factor TFIIB and the vitamin D receptor cooperatively activate ligand-dependent transcription.
Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1535-9
PMID: 7878015
-
Nuclear receptors enhance our understanding of transcription regulation.
Trends Genet. 1988 Nov;4(11):309-14
PMID: 2853466
-
Cloning, structure, and expression of the mitochondrial cytochrome P-450 sterol 26-hydroxylase, a bile acid biosynthetic enzyme.
J Biol Chem. 1989 May 15;264(14):8222-9
PMID: 2722778
-
A novel genetic system to detect protein-protein interactions.
Nature. 1989 Jul 20;340(6230):245-6
PMID: 2547163
-
Reconstitution of the vitamin D-responsive osteocalcin transcription unit in Saccharomyces cerevisiae.
Mol Cell Biol. 1989 Aug;9(8):3517-23
PMID: 2552296
-
Thyrotropin-induced expression of a gene for a ribosomal protein related to the trk oncogene.
Mol Cell Endocrinol. 1990 Jan 2;68(1):R25-30
PMID: 2303158
-
Transcriptional control by nuclear receptors.
FASEB J. 1991 Apr;5(7):2044-51
PMID: 2010057
-
Identification of novel steroid-response elements.
Gene Expr. 1992;2(1):39-47
PMID: 1617301
-
Members of the steroid hormone receptor superfamily interact with TFIIB (S300-II).
J Biol Chem. 1992 Sep 5;267(25):17617-23
PMID: 1517211
-
Kindred S thyroid hormone receptor is an active and constitutive silencer and a repressor for thyroid hormone and retinoic acid responses.
Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10633-7
PMID: 1359543
-
Multiple mechanisms of chicken ovalbumin upstream promoter transcription factor-dependent repression of transactivation by the vitamin D, thyroid hormone, and retinoic acid receptors.
J Biol Chem. 1993 Feb 25;268(6):4152-60
PMID: 8382695
-
The retinoblastoma protein associates with the protein phosphatase type 1 catalytic subunit.
Genes Dev. 1993 Apr;7(4):555-69
PMID: 8384581
-
The vitamin D receptor interacts with general transcription factor IIB.
J Biol Chem. 1995 Mar 3;270(9):4748-52
PMID: 7876247
-
The yeast SIN3 gene product negatively regulates the activity of the human progesterone receptor and positively regulates the activities of GAL4 and the HAP1 activator.
Mol Gen Genet. 1994 Dec 15;245(6):724-33
PMID: 7830720
-
Activation of the receptor kinase domain of the trk oncogene by recombination with two different cellular sequences.
EMBO J. 1988 Jan;7(1):147-54
PMID: 2966065
-
The steroid and thyroid hormone receptor superfamily.
Science. 1988 May 13;240(4854):889-95
PMID: 3283939
-
Interaction of human thyroid hormone receptor beta with transcription factor TFIIB may mediate target gene derepression and activation by thyroid hormone.
Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):8832-6
PMID: 8415616
-
Transcriptional activation by the estrogen receptor requires a conformational change in the ligand binding domain.
Mol Endocrinol. 1993 Oct;7(10):1266-74
PMID: 8264659
-
Modulation of gene expression by calreticulin binding to the glucocorticoid receptor.
Nature. 1994 Feb 3;367(6462):476-80
PMID: 8107808
-
Inhibition of nuclear hormone receptor activity by calreticulin.
Nature. 1994 Feb 3;367(6462):480-3
PMID: 8107809
-
Functional evidence for ligand-dependent dissociation of thyroid hormone and retinoic acid receptors from an inhibitory cellular factor.
Mol Cell Biol. 1994 Sep;14(9):5756-65
PMID: 8065310
-
Differential recognition of target genes by nuclear receptor monomers, dimers, and heterodimers.
Endocr Rev. 1994 Jun;15(3):391-407
PMID: 8076589
-
Human TAFII30 is present in a distinct TFIID complex and is required for transcriptional activation by the estrogen receptor.
Cell. 1994 Oct 7;79(1):107-17
PMID: 7923369
-
Mechanisms for synergistic activation of thyroid hormone receptor and retinoid X receptor on different response elements.
J Biol Chem. 1994 Dec 16;269(50):31436-42
PMID: 7989311
-
The tau 4 activation domain of the thyroid hormone receptor is required for release of a putative corepressor(s) necessary for transcriptional silencing.
Mol Cell Biol. 1995 Jan;15(1):76-86
PMID: 7799971
-
Specific binding of estrogen receptor to the estrogen response element.
Mol Cell Biol. 1989 Jan;9(1):43-9
PMID: 2927397