Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The morphogen retinoic acid (RA) regulates gene transcription by interacting with specific nuclear receptors that recognize DNA sequences near responsive promoters. While much has recently been learned about the nuclear receptor proteins, little is known about the genes that are directly regulated by RA and their cis-acting response elements recognized by these receptors. Here we have analyzed the RA receptor-beta (RAR beta) gene promoter that is controlled by RA. We find that a RA-responsive element (RARE) is located adjacent to the TATA box. The RARE shows a direct repeat symmetry which is essential for its function. While thyroid hormone-responsive elements can also function as RAR response elements, we show here that this RARE is activated by endogenous RARs and RAR beta, but cannot be regulated by thyroid hormone receptors and other known nuclear receptors. In addition, we find that RAR gamma is a poor activator of this RARE. However, the response element is bound with high affinity by both RAR beta and RAR gamma as well as by thyroid hormone receptors. Thus, interaction between specific response elements and receptors is insufficient for gene activation.
Mol Endocrinol 1990 Nov
PMID:A retinoic acid receptor-specific element controls the retinoic acid receptor-beta promoter. 217 41

A cDNA for the gene that encodes a human cytosolic thyroid hormone binding protein (p58) recently has been isolated and sequenced. Analysis of the p58 sequence indicates that it is identical to the subunit of pyruvate kinase, subtype M2. By in situ hybridization, the gene for p58 was mapped to 15q24-25. This localization shows that the p58 gene is not linked to the L-type of pyruvate kinase, which is located on chromosome 1. The p58 gene was found to be activated in several forms of cancer. Current localization will permit us to assess the effect of alterations involving chromosome 15 on the structure and activity of the p58 gene in neoplasms or chromosome syndromes.
Somat Cell Mol Genet 1990 Nov
PMID:Chromosomal localization of the gene for a human cytosolic thyroid hormone binding protein homologous to the subunit of pyruvate kinase, subtype M2. 226 32

The thyroid hormone 3,3',5-triiodothyronine (T3) plays an important role in the differentiation of adipocytes, as well as in the thermogenic activity of brown adipose tissue. Recently a T3 binding protein (T3BP), which is associated with plasma membranes, has been isolated and cloned from liver. It proved to be homologous to the multifunctional enzyme protein disulfide isomerase (PDI), which is involved in posttranslational modifications of secretory proteins. In this study we investigated the T3BP/PDI mRNA expression in white and brown adipose tissue of rat and bovine, as well as in several rodent adipose cell lines at various states of differentiation. T3BP/PDI mRNA expression was found in white and brown adipose tissue, as well as in preadipocytes and adipocytes at all states of differentiation. Comparison to other tissues (liver, kidney, heart, brain) revealed that its expression was highest in white fat. No modulation of T3BP/PDI mRNA corresponding to different adaptational or developmental situations could be detected in adipose tissue.
Mol Cell Endocrinol 1990 Oct 22
PMID:The mRNA of protein disulfide isomerase and its homologue the thyroid hormone binding protein is strongly expressed in adipose tissue. 226 93

The regulation of fibronectin (FN) gene expression by thyroid hormone was studied. Rats were rendered hypothyroid by thyroidectomy, and the administration of T4 or T3 was used to produce rats in various thyroid states. RNA was extracted from fresh liver, kidney, and heart, and FN mRNA was determined by dot blot hybridization with a 32P-labeled rat FN cDNA probe. The specificity of the hybridization was assessed by Northern blot analysis. In liver, thyroidectomy decreased the abundance of FN mRNA by half, and daily administration of physiological doses of T4 or T3 for 5-6 days restored FN mRNA to the control level. The administration of pharmacological doses of thyroid hormones induced a further increase in the abundance of FN mRNA. A significant dose-dependent correlation between serum levels of T4 and the abundance of FN mRNA was observed in liver. A receptor-saturating dose of T3 (200 micrograms) given to thyroidectomized rats produced a significant increase in FN mRNA within 6 h after injection, indicating that expression of the FN gene was induced relatively rapidly. Moreover, a nuclear run-off assay revealed that thyroid hormone induces expression of the FN gene at least in part at a transcriptional level. The amount of FN mRNA was also determined in kidney and heart of the same rats. Although the abundance of FN mRNA changed by thyroidectomy or the administration of thyroid hormone in those organs, the magnitude of changes were slight compared with those observed in liver. These results suggested that a marked and dose-dependent induction of the FN gene by thyroid hormone occurs specifically in liver.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1990 May
PMID:Specific induction of fibronectin gene in rat liver by thyroid hormone. 227 53

Conversion of the prohormone T4 to the active hormone T3 is catalyzed by 5'-deiodinases, enzymes that have not been purified. Previous studies have shown that modulating thyroid status results in changes in type I deiodinase activity in the rat liver. We have quantitated type I deiodinase mRNA in liver by an expression assay using Xenopus laevis oocytes. We report here that changes in enzyme activity correlate closely with changes in levels of the mRNA for this enzyme, indicating that thyroid hormone regulates type I deiodinase at a pretranslational step. Using the oocyte system to express size-fractionated mRNA, we have also determined that the mRNA coding for this protein is between 1.9-2.4 kilobases in length. It has been proposed that protein disulfide isomerase (PDI) is closely related to the rat type I 5'-deiodinase. Our results indicate that this is not the case, since injection of in vitro transcribed PDI mRNA into oocytes did not result in expression of deiodinase activity, and the deiodinase mRNA could be physically separated from the 2.8-kilobase mRNA species hybridizing to rat PDI cRNA by size fractionation.
Mol Endocrinol 1990 May
PMID:Thyroid hormone regulates type I deiodinase messenger RNA in rat liver. 227 56

Recent work has demonstrated that the unique post-transcriptional editing reaction which modifies mammalian apolipoprotein (apo) B100 mRNA, producing an in-frame stop codon in the modified (apo B48) transcript, is modulated in vivo in the rat liver by thyroid hormone (T3). We now report the results of studies undertaken to examine the effects of two synthetic T3 analogs and GH on apo B gene expression together with their effects on hepatic apo A-I, A-IV, C-III, and malic enzyme (ME)mRNAs. The T3 analogs were previously shown to exhibit similar binding to the hepatic nuclear T3 receptor (50% and 38% of native T3) but differing biopotency (18 and less than 3% of native T3). Apo B100 mRNA editing, determined by differential hybridization of polymerase chain reaction amplified apo B cDNA, demonstrated 50-56% unmodified (apo B100) mRNA in control and hypothyroid animals and this proportion was unaltered by GH (61% B100 mRNA), despite a reduction in apo B100 synthesis. Both T3 analogs altered apo B mRNA editing (12-16% B100 mRNA) and no apo B100 synthesis was detectable in vivo. Additionally, both T3 analogs produced a 4- to 10-fold induction in hepatic apo A-I and A-IV mRNA abundance, similar to the effects of native T3. GH produced no alteration in apo A-I or A-IV mRNA abundance and neither T3 analog, GH, or native T3 produced a change in apo C III mRNA abundance.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1990 May
PMID:Apolipoprotein B mRNA editing is modulated by thyroid hormone analogs but not growth hormone administration in the rat. 227 57

We have examined the binding of nuclear proteins and recombinant thyroid hormone receptors (TRs) to the palindromic thyroid hormone responsive element AGGTCATGACCT (TREp) using a gel electrophoretic mobility shift assay. Four specific protein-DNA complexes were detected after incubation of nuclear extracts (NE) from T3-responsive pituitary (GH3) cells with a TREp-containing DNA fragment. This was compared with the TREp binding of reticulocyte lysate-synthesized TRs. TR alpha 1 and TR beta 2 each formed a single major TR:TREp complex which comigrated with the least retarded complex formed by GH3 NE, while TR beta 1 formed multiple complexes suggesting that it can bind to TREp as an oligomer. Interestingly, coincubation of 35S-TR alpha 1, GH3 NE, and unlabeled TREp resulted in not only the 35S-TR:TREp complex, but in two additional more greatly retarded complexes containing 35S-TR alpha 1 and comigrating with those formed by GH3 extract alone. Incubation of each of the TRs with NE from COS-7 cells, which do not possess sufficient endogenous TRs to mediate T3-responses, resulted in formation of a new, more greatly shifted complex. A similar, heat labile activity which altered mobility of the TR:TRE complex was also present in NE from T3-unresponsive JEG-3 cells. At high concentration of NE, all of the TR bound to TREp was more greatly retarded than in the absence of NE. Truncation of TR alpha 1 at amino acid 210 prevented additional complex formation in the presence of NE without affecting DNA binding, suggesting that the carboxyl-terminus of the TRs is essential for interaction with nuclear proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1990 Nov
PMID:Thyroid hormone receptors form distinct nuclear protein-dependent and independent complexes with a thyroid hormone response element. 228 Jul 69

In the present study we have examined the effect of the general anesthetic agent sodium pentobarbital (given i.p. to the intact animal) on the hemodynamic function of the isolated perfused heart and its response to treatments which affect calcium transsarcolemmal influx: extracellular calcium concentration and thyroid hormone. Perfused hearts (modified Langendorff system) isolated from anesthetized rats were found to respond differently to the two aforementioned effectors than hearts excised from non-anesthetized animals. Hearts of the two groups demonstrated a gradual increase in inotropic activity in response to step-wise increase in calcium concentration in the perfusion medium. However, cardiac contractility and the pattern of the response to the gradual increase in calcium concentration were different. At the lower Ca2+ concentrations of 0.5 and 1.0 mM, inotropic activity (left ventricular systolic pressure (LVP) and +dP/dt values) of hearts from anesthetized animals was significantly greater (P less than 0.05) than that of hearts from non-anesthetized animals: LVP values (mmHg, mean +/- S.E.M.) in hearts from anesthetized an non-anesthetized rats were: at 0.5 mM Ca2+, 19 +/- 3 and 9 +/- 2; and at 1.0 mM, 103 +/- 12 and 76 +/- 6, respectively. At the higher Ca2+ concentrations, hearts from anesthetized animals demonstrated maximal LVP at 1.75 mM calcium (139 +/- 9 mmHg), whereas the LVP values in hearts from non-anesthetized animals continued to increase throughout all the Ca2+ concentrations employed. A similar pattern of response was observed for +dP/dt values.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Cell Cardiol 1990 Nov
PMID:Effect of anesthesia on cardiac function and response in the perfused rat heart. 228 88

When a human fetal muscle cDNA library was screened with the human thyroid hormone receptor alpha 2 cDNA at low stringency, we found a weakly hybridizing cDNA. The sequence of the insert was 2498 basepairs, with an open reading frame of 1794 basepairs encoding a protein of 598 amino acids and a predicted molecular mass of 64 kDa. The DNA-binding domain and the ligand-binding domain are similar to those of steroid and thyroid hormone receptors. Moreover, this cDNA is highly homologous to mouse nur77 and rat NGFI-B, which are early response genes induced by nerve growth factor and other serum growth factors. We designated this gene NAK1. The modulation of expression of NAK1 during stimulation of cell growth was studied. The mRNA of NAK1 was induced rapidly and transiently by growth-stimulating agents, such as adenosine diphosphate, in monkey kidney cells (BSC-1), by phytohemagglutinin in human lymphocytes, and by serum stimulation of arrested fibroblasts. It is expressed in human fetal muscle and adult liver, brain, and thyroid. NAK1 could be a nuclear receptor. It will be of great interest to determine the ligand for NAK1 and the genes that are regulated by it.
Mol Endocrinol 1990 Oct
PMID:A human early response gene homologous to murine nur77 and rat NGFI-B, and related to the nuclear receptor superfamily. 228 97

Multiple forms of human thyroid hormone (T3) receptor have been identified, including true receptors that bind T3 (alpha 1 and beta) and a splicing variant (alpha 2) that does not bind T3. The alpha 1- and beta-receptors activate transcription through interactions with positive thyroid response elements (TREs). The alpha 2 variant is unable to activate transcription and has been reported to inhibit alpha 1 or beta stimulation of positive TREs, a property referred to as dominant negative activity. In this report we have performed studies to assess the functional properties of different members of the thyroid receptor family with regard to both positive and negative transcriptional regulation. The alpha 1-, alpha 2-, and beta-receptors were each coexpressed in JEG-3 cells with either TreTKCAT (CAT = chloramphenicol acetyltransferase), a reporter gene that contains a positive TRE, or TSH alpha CAT, a negatively regulated reporter gene. The alpha 1 and beta isoforms stimulated transcription of TreTKCAT and inhibited TSH alpha CAT transcription in a T3-dependent manner, whereas the alpha 2 variant was inactive. When coexpressed with alpha 1- or beta-receptors, alpha 2 inhibited regulation of positive TREs, but the effects of alpha 2 were modest and only occurred when relatively high doses of receptor were transfected. The alpha 2-receptor variant did not affect negative regulation by alpha 1- or beta-receptors. Thus, in both positive and negative regulation, thyroid hormone receptor isoforms that bind T3 (alpha 1, beta) are functional, whereas the alpha 2 isoform, which does not bind T3, is not functional.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1990 Oct
PMID:Negative and positive transcriptional regulation by thyroid hormone receptor isoforms. 228


<< Previous 1 2 3 4 5 6 7 8 9 10