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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peroxisome proliferator activated receptors are ligand activated transcription factors belonging to the nuclear hormone receptor superfamily. Three cDNAs encoding such receptors have been isolated from Xenopus laevis (xPPAR alpha, beta, and gamma). Furthermore, the gene coding for xPPAR beta has been cloned, thus being the first member of this subfamily whose genomic organization has been solved. Functionally, xPPAR alpha as well as its mouse and rat homologs are thought to play an important role in lipid metabolism due to their ability to activate transcription of a reporter gene through the promoter of the acyl-CoA oxidase (ACO) gene. ACO catalyzes the rate limiting step in the peroxisomal beta-oxidation of fatty acids. Activation is achieved by the binding of xPPAR alpha on a regulatory element (DR1) found in the promoter region of this gene, xPPAR beta and gamma are also able to recognize the same type of element and are, as PPAR alpha, able to form heterodimers with retinoid X receptor. All three xPPARs appear to be activated by synthetic peroxisome proliferators as well as by naturally occurring fatty acids, suggesting that a common mode of action exists for all the members of this subfamily of nuclear hormone receptors.
J Steroid Biochem Mol Biol 1993 Dec
PMID:Xenopus peroxisome proliferator activated receptors: genomic organization, response element recognition, heterodimer formation with retinoid X receptor and activation by fatty acids. 827 43

Retinoic acid (RA) treatment of human embryonal carcinoma (EC) NTera-2 (NT2) cells induces expression of major histocompatibility complex (MHC) class I and beta-2 microglobulin surface molecules. We found that this induction was accompanied by increased levels of MHC class I mRNA, which was attributable to the activation of the two conserved upstream enhancers, region I (NF-kappa B like) and region II. This activation coincided with the induction of nuclear factor binding activities specific for the two enhancers. Region I binding activity was not present in undifferentiated NT2 cells, but binding of an NF-kappa B heterodimer, p50-p65, was induced following RA treatment. The p50-p65 heterodimer was produced as a result of de novo induction of p50 and p65 mRNAs. Region II binding activity was present in undifferentiated cells at low levels but was greatly augmented by RA treatment because of activation of a nuclear hormone receptor heterodimer composed of the retinoid X receptor (RXR beta) and the RA receptor (RAR beta). The RXR beta-RAR beta heterodimer also bound RA responsive elements present in other genes which are likely to be involved in RA triggering of EC cell differentiation. Furthermore, transfection of p50 and p65 into undifferentiated NT2 cells synergistically activated region I-dependent MHC class I reporter activity. A similar increase in MHC class I reporter activity was demonstrated by cotransfection of RXR beta and RAR beta. These data show that following RA treatment, heterodimers of two transcription factor families are induced to bind to the MHC enhancers, which at least partly accounts for RA induction of MHC class I expression in NT2 EC cells.
Mol Cell Biol 1993 Oct
PMID:Retinoic acid induction of major histocompatibility complex class I genes in NTera-2 embryonal carcinoma cells involves induction of NF-kappa B (p50-p65) and retinoic acid receptor beta-retinoid X receptor beta heterodimers. 841 17

Rev-ErbA alpha (Rev-Erb) is a nuclear hormone receptor-related protein encoded on the opposite strand of the alpha-thyroid hormone receptor (TR) gene. This unusual genomic arrangement may have a regulatory role, but the conservation of human and rodent Rev-Erb amino acid sequences suggests that the protein itself has an important function, potentially as a sequence-specific transcriptional regulator. However, despite its relationship to the TR, Rev-Erb bound poorly to TR binding sites. To determine its DNA-binding specificity in an unbiased manner, Rev-Erb was synthesized in Escherichia coli, purified, and used to select specific binding-sites from libraries of random double-stranded DNA sequences. We found that Rev-Erb binds to a unique site consisting of a specific 5-bp A/T-rich sequence adjacent to a TR half-site. Rev-Erb contacts this entire asymmetric 11-bp sequence, which is the longest nonrepetitive element specifically recognized by a member of the thyroid/steroid hormone receptor superfamily, and mutations in either the A/T-rich or TR half-site regions abolished specific binding. The binding specificity of wild-type Rev-Erb was nearly identical to that of C- and N-terminally truncated forms. This binding was not enhanced by retinoid X receptor, TR, or other nuclear proteins, none of which formed heterodimers with Rev-Erb. Rev-Erb also appeared to bind to the selected site as a monomer. Furthermore, Rev-Erb activates transcription through this binding site even in the absence of exogenous ligand. Thus, Rev-Erb is a transcriptional activator whose properties differ dramatically from those of classical nuclear hormone receptors, including the TR encoded on the opposite strand of the same genomic locus.
Mol Cell Biol 1993 May
PMID:The orphan receptor Rev-ErbA alpha activates transcription via a novel response element. 847 64

Several regulatory interactions between the AP-1 and the nuclear hormone receptor families of transcription factors have been reported. However, the molecular mechanisms that underlie these interactions remain unknown, and models derived from transient-transfection experiments are contradictory. We have investigated the effect of the purified glucocorticoid receptor (GR) DNA-binding domain (GR residues 440 to 533 [GR440-533]) on DNA binding and transcription activation by Fos-Jun heterodimers and Jun homodimers. GR440-533 differentially inhibited DNA binding and transcription activation by Fos-Jun heterodimers. Inhibition of Jun homodimers required a 10-fold-higher concentration of GR440-533. An excess of Fos monomers protected Fos-Jun heterodimers from inhibition by GR440-533. Surprisingly, regions outside the leucine zipper and basic region were required for GR inhibition of Fos and Jun DNA binding. The region of GR440-533 required for inhibition of Fos-Jun DNA binding was localized to the zinc finger DNA-binding domain. However, inhibition of Fos-Jun DNA binding was independent of DNA binding by GR440-533. GR440-533 also differentially inhibited Fos-Jun heterodimer binding to the proliferin plfG element. Differential inhibition of DNA binding by different AP-1 family complexes provides a potential mechanism for the diverse interactions between nuclear hormone receptors and AP-1 family proteins at different promoters and in different cell types.
Mol Cell Biol 1993 Jun
PMID:Fos is a preferential target of glucocorticoid receptor inhibition of AP-1 activity in vitro. 849 79

DAX-1, an orphan member of the nuclear hormone receptor superfamily, is responsible for X-linked adrenal hypoplasia congenita (AHC) and the frequently associated hypogonadotropic hypogonadism (HH). The entire DAX-1 genomic region has been sequenced and a putative steroidogenic factor-1 response element has been identified in the promoter region of the gene. The purpose of these investigations was to determine if DAX-1 was expressed in the central nervous system, particularly the hypothalamus and pituitary, in order to better understand the relationship of mutations in this gene to HH associated with AHC. We used Northern blot analysis and reverse transcription PCR to demonstrate that DAX-1 was expressed in the hypothalamus and the pituitary, and to confirm its expression in adrenal cortex and gonads. The expression of DAX-1 in these tissues indicates the involvement of DAX-1 in the development of the reproductive system at multiple levels within the hypothalamic-pituitary-adrenal/gonadal axis. We also observed the expression of DAX-1 in a human adrenocortical carcinoma cell line, NCI-H295, that has features characteristic of the fetal adrenal cortex. Therefore, NCI-H295 cells will be a useful cellular model for investigating the involvement of DAX-1 in the regulation of steroidogenesis.
Biochem Mol Med 1995 Oct
PMID:Expression of DAX-1, the gene responsible for X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism, in the hypothalamic-pituitary-adrenal/gonadal axis. 859 42

The 26S proteasome complex plays a general role in turnover of both short and long lived proteins by specifically degrading ubiquitinated proteins. Recent evidence suggests that this large protease has more specific functions in a number of important cellular processes, ranging from activation of the transcription factor NFkB and antigen processing to transit through mitosis. We have identified a component of the 26S proteasome that interacts specifically with MB67, an orphan member of the nuclear hormone receptor superfamily. MIP224 (MB67 interacting protein) was isolated using the yeast two hybrid system and is apparently identical to the human 26S proteasome component TBP7. MIP224/TBP7 is one of several proteasomal proteins that share a strongly conserved ATPase domain (CAD) which is also present in a rapidly expanding superfamily of proteins with diverse functions. In yeast, MIP224 interacts specifically with MB67 and another closely related orphan receptor, but does not interact with several other receptor superfamily members tested. In mammalian cells, coexpression of MIP224 inhibits transactivation by MB67. MIP224 also interacts in yeast with other CAD proteins, including MSS1, which is proteasomal, and TRIP1, which is associated with transcriptional activation. This interaction of a proteasomal protein with a transcriptional protein suggests a previously unexpected link between the processes of protein degradation and transcriptional regulation.
J Steroid Biochem Mol Biol 1996 Jan
PMID:A component of the 26S proteasome binds on orphan member of the nuclear hormone receptor superfamily. 860 43

Peroxisome proliferator-response elements (PPRE) are cis-acting regulatory elements that confer responsiveness to peroxisome proliferators and various fatty acids by serving as target sites for ligand-activated peroxisome proliferator-activated receptor (PPAR)/retinoid X receptor (RXR) heterodimers. Other cellular factors, including additional nuclear hormone receptors, also interact with PPREs and modulate PPAR function. We have developed a positive selection strategy in yeast to identify mammalian factors that functionally interact with PPREs. Saccharomyces cerevisiae containing an integrated copy of the HIS3 gene under transcriptional control of a minimal CYC1 promoter and two copies of the rat enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase PPRE was constructed and transformed with a rat liver cDNA yeast expression library. Plasmids were isolated from his + transformants. One plasmid contained a cDNA encoding the complete rat chicken ovalbumin upstream promoter transcription factor II (COUP-TFII), an orphan member of the nuclear hormone receptor superfamily. COUP-TFII potently activated PPRE-linked reporter gene expression in yeast, and COUP-TFII synthesized in yeast or in vitro formed specific protein/DNA complexes with this PPRE. Significantly, COUP-TFII did not activate transcription of PPRE-linked reporter genes in mammalian cells but rather strongly inhibited induction mediated by PPAR/RXR. Our findings demonstrate the utility of using genetic screening in yeast to identify sequence-specific DNA binding transcription factors.
Mol Cell Endocrinol 1996 Jun 18
PMID:Identification of COUP-TFII as a peroxisome proliferator response element binding factor using genetic selection in yeast: COUP-TFII activates transcription in yeast but antagonizes PPAR signaling in mammalian cells. 880 36

Nuclear hormone receptors are the largest known family of eukaryotic transcription factors and serve as critical effectors of vertebrate homeostasis, growth, and differentiation. The precise transcriptional response mediated by a given nuclear hormone receptor is dictated by hormone, promoter, and cellular context, and many nuclear hormone receptors function bimodally as both transcriptional activators and repressors. We report here the identification of a family of proteins, denoted TRACs (T3 receptor-associating cofactors), which physically interact with nuclear hormone receptors and can modulate the transcriptional properties of these receptors. TRACs associate with retinoic acid, retinoid X, and thyroid hormone receptors, as well as the PML-RAR alpha and v-Erb A oncoproteins. Certain TRAC forms attenuate target gene expression and may serve as corepressors, whereas other TRAC family members appear to counteract these effects. We suggest that TRACs and related cofactors may participate in dictating the pleiotropic transcriptional capacities of the nuclear hormone receptors.
Mol Endocrinol 1996 Jul
PMID:Identification of TRACs (T3 receptor-associating cofactors), a family of cofactors that associate with, and modulate the activity of, nuclear hormone receptors. 881 22

The transcription factor FTZ-F1 is a member of the nuclear hormone receptor superfamily and is transiently expressed during the mid- and late prepupal periods in Drosophila melanogaster. A putative pupal cuticle gene, EDG84A, is expressed slightly following FTZ-F1 expression during the prepupal period and carries a strong FTZ-F1 binding site between bases 100 and 92 upstream of its transcription start site. In this study, EDG84A mRNA was found to be prematurely expressed upon heat induction of FTZ-F1 in prepupae carrying the heat shock promoter-FTZ-F1 cDNA fusion gene construct. Transgenic fly lines having the 0.8-kb region of the EDG84A promoter fused to lacZ expressed the reporter gene in a tissue- and stage-specific manner. Base substitutions in the FTZ-F1 binding site within the 0.8-kb promoter abolished expression of lacZ. These results strongly suggest that the EDG84A gene is a direct target of FTZ-F1. Deletion studies of the cis-regulatory region of the EDG84A gene revealed that space-specific expression in imaginal disc-derived epidermis is controlled by the region between bp -408 and -104 from the transcription start site. The region between bp -408 and -194 is necessary to repress expression in a posterior part of the body, while the region between bp -193 and -104 carries a positive element for activation in an anterior part of the body. These results suggest that FTZ-F1 governs expression of the EDG84A gene in conjunction with putative tissue-specific regulators.
Mol Cell Biol 1996 Nov
PMID:Regulation of the EDG84A gene by FTZ-F1 during metamorphosis in Drosophila melanogaster. 888 79

The thyroid hormone receptor (TR) and the retinoic acid receptor (RAR) act as transcriptional repressors when they are not occupied by their cognate ligands. This repressor function is mediated by proteins called corepressors. One of the nuclear hormone receptor corepressors, N-CoR, was originally isolated as a retinoid X receptor-interacting protein called RIP13. We have isolated a new potential variant of RIP13/N-CoR that is missing previously described transcriptional repressor domains but is similar in structure to the related corepressor termed SMRT or TRAC-2. Detailed analysis of the interaction with TR and RAR demonstrates that RIP13/N-CoR contains a new receptor interaction domain, termed ID-II, in addition to the previously described domain, referred to here as ID-I. Both ID-I and ID-II are capable of interacting independently with either TR or RAR, as assessed by the yeast two-hybrid system, by a mammalian two-hybrid system, or by direct in vitro binding. Results with all three approaches confirm that RIP13/N-CoR also interacts with retinoid X receptor, but this interaction is weaker than that with TR or RAR. Together, these results demonstrate that RIP13/N-CoR can interact with several different nuclear hormone receptors via two separate receptor interaction domains. Differences between the interactions observed in the different systems suggest that corepressor function may be modified by additional factors present in various cell types.
Mol Endocrinol 1996 Dec
PMID:Two receptor interacting domains in the nuclear hormone receptor corepressor RIP13/N-CoR. 896 Dec 73


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