scholarly journals Human ERRγ, a Third Member of the Estrogen Receptor-Related Receptor (ERR) Subfamily of Orphan Nuclear Receptors: Tissue-Specific Isoforms Are Expressed during Development and in the Adult

2000 ◽  
Vol 14 (3) ◽  
pp. 382-392 ◽  
Author(s):  
David J. Heard ◽  
Peder L. Norby ◽  
Jim Holloway ◽  
Henrik Vissing
Keyword(s):  
Estrogen Receptor ◽  
Nuclear Receptors ◽  
Expression Patterns ◽  
Protein Isoforms ◽  
Hek293 Cells ◽  
Receptor Protein ◽  
Orphan Nuclear Receptors ◽  
Independent Manner ◽  
Tissue Specific ◽  
Alternatively Spliced

Abstract The nuclear receptor protein superfamily is a large group of transcription factors involved in many aspects of animal development, tissue differentiation, and homeostasis in the higher eukaryotes. A subfamily of receptors, ERRα and β (estrogen receptor-related receptor α and β), closely related to the ER, were among the first orphan nuclear receptors identified. These receptors can bind DNA as monomers and are thought to activate transcription constitutively, unaffected by β-estradiol. Studies of the expression patterns of ERRα and gene disruption experiments of ERRβ indicate that they play an important role in the development and differentiation of specific tissues in the mouse. In this work we demonstrate the existence in humans of a third member of this subfamily of receptors, termed ERRγ, which is highly expressed in a number of diverse fetal and adult tissues including brain, kidney, pancreas, and placenta. The ERRγ mRNA is highly alternatively spliced at the 5′-end, giving rise to a number of tissue-specific RNA species, some of which code for protein isoforms differing in the N-terminal region. Like ERRα andβ , ERRγ binds as a monomer to an ERRE. A GAL4-ERRγ fusion protein activates transcription in a ligand-independent manner in transfected HEK293 cells to a greater degree than either the GAL4-ERRα or -β fusion proteins.

Tissue-specific expression patterns of nuclear receptors

2013 ◽  
Author(s):  
AL Bookout ◽  
Y Jeong ◽  
M Downes ◽  
RT Yu ◽  
RM Evans ◽  
...  
Keyword(s):  
Nuclear Receptors ◽  
Expression Patterns ◽  
Specific Expression ◽  
Tissue Specific ◽  
Tissue Specific Expression

Differential expression of Broad-Complex transcription factors may forecast tissue-specific developmental fates during Drosophila metamorphosis

Development ◽  
1994 ◽  
Vol 120 (11) ◽  
pp. 3275-3287 ◽  
Author(s):  
I.F. Emery ◽  
V. Bedian ◽  
G.M. Guild
Keyword(s):  
Western Blot ◽  
Expression Patterns ◽  
Primary Response ◽  
Protein Isoforms ◽  
Secondary Response ◽  
C Protein ◽  
Tissue Specific ◽  
Specific Outcome ◽  
C Proteins ◽  
Broad Complex

The steroid hormone ecdysone initiates metamorphosis in Drosophila melanogaster by activating a cascade of gene activity that includes primary response transcriptional regulators and secondary response structural genes. The Broad-Complex (BR-C) primary response gene is composed of several distinct genetic functions and encodes a family of related transcription factor isoforms. Our objective was to determine whether BR-C isoforms were components of the primary ecdysone response in all tissues and whether tissue-specific isoform expression is associated with tissue-specific metamorphic outcomes. We used specific antibody reagents that recognize and distinguish among the Z1, Z2 and Z3 BR-C protein isoforms to study protein expression patterns during the initial stages of metamorphosis. Western blot analyses demonstrated that BR-C isoforms are induced at the onset of metamorphosis, each with unique kinetics of induction and repression. Whole-mount immunostaining showed that the BR-C proteins accumulate in the nuclei of all larval and imaginal tissues indicating that the BR-C is induced as a primary response in many tissues. Several tissues express different levels and combinations of the BR-C isoforms suggesting that the BR-C is important in determining the tissue-specific outcome of many parallel ecdysone response cascades. For example, prepupal salivary glands (destined for histolysis during metamorphosis) express Z1 isoforms while imaginal discs (destined for cell differentiation and morphogenesis) shift from the synthesis of Z2 isoforms to the synthesis of Z1 isoforms. The prepupal central nervous system (destined for tissue remodeling) expresses all isoforms, with Z3 predominating. Salivary gland chromosome immunostaining indicated that BR-C proteins interact directly with numerous loci in the polytene genome. Finally, western blot analyses showed that distinct BR-C genetic functions can be correlated with single and specific BR-C protein isoforms.

scholarly journals Function of Nr4a Orphan Nuclear Receptors in Proliferation, Apoptosis and Fuel Utilization Across Tissues

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1373 ◽  
Author(s):  
Herring ◽  
Elison ◽  
Tessem
Keyword(s):  
Transcription Factors ◽  
Family Member ◽  
Nuclear Receptors ◽  
Hormone Receptors ◽  
Cellular Proliferation ◽  
Nuclear Hormone Receptors ◽  
Fuel Utilization ◽  
Orphan Nuclear Receptors ◽  
Tissue Specific ◽  
Specific Effects

The Nr4a family of nuclear hormone receptors is composed of three members—Nr4a1/Nur77, Nr4a2/Nurr1 and Nr4a3/Nor1. While currently defined as ligandless, these transcription factors have been shown to regulate varied processes across a host of tissues. Of particular interest, the Nr4a family impinge, in a tissue dependent fashion, on cellular proliferation, apoptosis and fuel utilization. The regulation of these processes occurs through both nuclear and non-genomic pathways. The purpose of this review is to provide a balanced perspective of the tissue specific and Nr4a family member specific, effects on cellular proliferation, apoptosis and fuel utilization.

Expression of estrogen receptor-related receptors, a subfamily of orphan nuclear receptors, as new tumor biomarkers in ovarian cancer cells

2005 ◽  
Vol 83 (6) ◽  
pp. 457-467 ◽  
Author(s):  
Pengming Sun ◽  
Jalid Sehouli ◽  
Carsten Denkert ◽  
Alexander Mustea ◽  
Dominique Könsgen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Nuclear Receptors ◽  
Ovarian Cancer Cells ◽  
Tumor Biomarkers ◽  
Orphan Nuclear Receptors

Orphan Nuclear Receptors in Reproduction: Lessons from Tissue-Specific Knockout Mice.

2011 ◽  
Vol 85 (Suppl_1) ◽  
pp. 161-161
Author(s):  
Cong Zhang ◽  
Kalyne Bertolin ◽  
Raj Duggavathi ◽  
Bruce D. Murphy
Keyword(s):  
Nuclear Receptors ◽  
Knockout Mice ◽  
Orphan Nuclear Receptors ◽  
Tissue Specific

Tissue-specific expression of two alternatively spliced isoforms of the human insulin receptor protein

1994 ◽  
Vol 31 (2) ◽  
pp. 59-65 ◽  
Author(s):  
G. Sesti ◽  
A. N. Tullio ◽  
R. D'Alfonso ◽  
M. L. Napolitano ◽  
M. A. Marini ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Human Insulin ◽  
Receptor Protein ◽  
Specific Expression ◽  
Tissue Specific ◽  
Tissue Specific Expression ◽  
Human Insulin Receptor ◽  
Alternatively Spliced

scholarly journals Down but not out? A novel protein isoform of the estrogen receptor alpha is expressed in the estrogen receptor alpha knockout mouse

2002 ◽  
Vol 29 (3) ◽  
pp. 281-286 ◽  
Author(s):  
M Kos ◽  
S Denger ◽  
G Reid ◽  
KS Korach ◽  
F Gannon
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptor Alpha ◽  
Binding Capacity ◽  
Protein Isoforms ◽  
Uterine Tissue ◽  
Receptor Alpha ◽  
Mrna Variants ◽  
Alternatively Spliced ◽  
Protein Isoform ◽  
And Function

The mouse knockout of the estrogen receptor alpha (ERalpha) gene, known as alphaERKO, has been extensively used for several years to study the role and function of ERalpha. Residual estradiol binding capacity in uterine tissue of 5-10% raised doubts if this knockout is a genuine null mutation of ERalpha. Although alternatively spliced ERalpha mRNA variants in the alphaERKO mouse were reported previously, the corresponding protein isoforms have not been detected to date. Here we show that a variant ERalpha protein, 61 kDa in size, is expressed in the uterine tissue of alphaERKO mice as a result of an alternative splicing. The transactivation capability of this protein is cell dependent and can be as high as 75% of the wild type ERalpha.

scholarly journals Evolutionary conservation of the structure and expression of alternatively spliced Ultrabithorax isoforms from Drosophila.

Genetics ◽  
1994 ◽  
Vol 136 (3) ◽  
pp. 965-977
Author(s):  
H M Bomze ◽  
A J López
Keyword(s):  
Alternative Splicing ◽  
Protein Function ◽  
Developmental Regulation ◽  
Expression Patterns ◽  
Proximal Region ◽  
Amino Acid Sequences ◽  
Drosophila Virilis ◽  
Protein Isoforms ◽  
Developmentally Regulated ◽  
Alternatively Spliced

Abstract In Drosophila melanogaster, alternatively spliced mRNAs from the homeotic gene Ultrabithorax (Ubx) encode a family of structurally distinct homeoprotein isoforms. The developmentally regulated expression patterns of these isoforms suggest that they have specialized stage- and tissue-specific functions. To evaluate the functional importance of UBX isoform diversity and gain clues to the mechanism that regulates processing of Ubx RNAs, we have investigated whether the Ubx RNAs of other insects undergo similar alternative splicing. We have isolated and characterized Ubx cDNA fragments from D. melanogaster, Drosophila pseudoobscura, Drosophila hydei and Drosophila virilis, species separated by as much as 60 million years of evolution, and have found that three aspects of Ubx RNA processing have been conserved. (1) These four species exhibit identical patterns of optional exon use in a region adjacent to the homeodomain. (2) These four species produce the same family of UBX protein isoforms with identical amino acid sequences in the optional exons, even though the common amino-proximal region has undergone substantial divergence. The nucleotide sequences of the optional exons, including third positions of rare codons, have also been conserved strongly, suggesting functional constraints that are not limited to coding potential. (3) The tissue- and stage-specific patterns of expression of different UBX isoforms are identical among these Drosophila species, indicating that the developmental regulation of the alternative splicing events has also been conserved. These findings argue for an important role of alternative splicing in Ubx function. We discuss the implications of these results for models of UBX protein function and the mechanism of alternative splicing.

Interplay between liganded and orphan nuclear receptors controls reproductive pathways

2000 ◽  
Vol 78 (3) ◽  
pp. 345-358 ◽  
Author(s):  
Raphaël Métivier ◽  
Yves Le Dréan ◽  
Gilles Salbert ◽  
Farzad Pakdel
Keyword(s):  
Estrogen Receptor ◽  
Transcriptional Regulation ◽  
Transcription Factors ◽  
Cell Fate ◽  
Nuclear Receptors ◽  
Gene Transcription ◽  
Transcription Rate ◽  
Orphan Nuclear Receptors ◽  
Estrogen Binding ◽  
Small Hydrophobic

Nuclear receptors are transcription factors that belong to an evolutionary ancient superfamily. These proteins, which are even present in primitive metazoans, are implicated in all levels of cell fate: proliferation, differentiation, and apoptosis. Some of these nuclear receptors behave as ligand-inducible transcription factors, as they have acquired during evolution the ability to bind ligands. This is the case for some proteins that recognize small hydrophobic signaling molecules, and particularly the estrogen receptor (ER or NR3A1), which regulates the target gene's transcription rate under estrogen binding. It is now known that the ER alone regulates the transcription of many genes, such as those implicated in reproductive functions. However, this ER-mediated signaling pathway could be modulated by other transcription factors. Our work has established that two other orphan nuclear receptors (SF-1 or NR5A1 and the COUP-TFs, NR2F1 and NR2F2) can enhance two ER-regulated genes implicated in salmonid reproductive functions: the ER gene itself, and the sGTHIIβ gene. Moreover, some xenoestrogens could disturb these regulations. Therefore, our data contribute to the concept that interplay between nuclear receptors is an important event for the transcriptional regulation of genes controlling cellular functions.Key words: reproduction, estrogen receptor, SF-1, COUP-TFI, gene transcription, xenobiotics.

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