scholarly journals The interface of nuclear and membrane steroid signaling

Endocrinology ◽  
2021 ◽  
Author(s):  
Lindsey S Treviño ◽  
Daniel A Gorelick
Keyword(s):  
Estrogen Receptor ◽  
Transcription Factors ◽  
Membrane Proteins ◽  
Cell Membrane ◽  
Nuclear Receptors ◽  
Cell Nucleus ◽  
Androgen Receptors ◽  
Steroid Receptors ◽  
And Function

Abstract Steroid hormones bind receptors in the cell nucleus and in the cell membrane. The most widely studied class of steroid hormone receptors are the nuclear receptors, named for their function as ligand-dependent transcription factors in the cell nucleus. Nuclear receptors, such as estrogen receptor alpha, can also be anchored to the plasma membrane, where they respond to steroids by activating signaling pathways independent of their function as transcription factors. Steroids can also bind integral membrane proteins, such as the G protein-coupled estrogen receptor. Membrane estrogen and progestin receptors have been cloned and characterized in vitro and influence the development and function of many organ systems. Membrane androgen receptors were cloned and characterized in vitro, but their function as androgen receptors in vivo is unresolved. We review the identity and function of membrane proteins that bind estrogens, progestins and androgens. We discuss evidence that membrane glucocorticoid and mineralocorticoid receptors exist, and whether glucocorticoid and mineralocorticoid nuclear receptors act at the cell membrane. In many cases, integral membrane steroid receptors act independently of nuclear steroid receptors, even though they may share a ligand.

scholarly journals Activating Signal Cointegrator 2 Belongs to a Novel Steady-State Complex That Contains a Subset of Trithorax Group Proteins

2003 ◽  
Vol 23 (1) ◽  
pp. 140-149 ◽  
Author(s):  
Young-Hwa Goo ◽  
Young Chang Sohn ◽  
Dae-Hwan Kim ◽  
Seung-Whan Kim ◽  
Min-Jung Kang ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Steady State ◽  
Nuclear Receptors ◽  
Transcriptional Activation ◽  
Retinoic Acid Receptor ◽  
Dependent Manner ◽  
Trithorax Group ◽  
Trithorax Group Proteins

ABSTRACT Many transcription coactivators interact with nuclear receptors in a ligand- and C-terminal transactivation function (AF2)-dependent manner. These include activating signal cointegrator 2 (ASC-2), a recently isolated transcriptional coactivator molecule, which is amplified in human cancers and stimulates transactivation by nuclear receptors and numerous other transcription factors. In this report, we show that ASC-2 belongs to a steady-state complex of approximately 2 MDa (ASC-2 complex [ASCOM]) in HeLa nuclei. ASCOM contains retinoblastoma-binding protein RBQ-3, α/β-tubulins, and trithorax group proteins ALR-1, ALR-2, HALR, and ASH2. In particular, ALR-1/2 and HALR contain a highly conserved 130- to 140-amino-acid motif termed the SET domain, which was recently implicated in histone H3 lysine-specific methylation activities. Indeed, recombinant ALR-1, HALR, and immunopurified ASCOM exhibit very weak but specific H3-lysine 4 methylation activities in vitro, and transactivation by retinoic acid receptor appears to involve ligand-dependent recruitment of ASCOM and subsequent transient H3-lysine 4 methylation of the promoter region in vivo. Thus, ASCOM may represent a distinct coactivator complex of nuclear receptors. Further characterization of ASCOM will lead to a better understanding of how nuclear receptors and other transcription factors mediate transcriptional activation.

scholarly journals Effect of lycorine on the structure and function of hepatoma cell membrane in vitro and in vivo

2020 ◽  
Vol 34 (1) ◽  
pp. 104-114 ◽  
Author(s):  
Guosong Xin ◽  
Miao Yu ◽  
Yang Hu ◽  
Shiyong Gao ◽  
Zheng Qi ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Hepatoma Cell ◽  
Structure And Function ◽  
And Function

scholarly journals Coactivator Proteins as Determinants of Estrogen Receptor Structure and Function: Spectroscopic Evidence for a Novel Coactivator-Stabilized Receptor Conformation

2005 ◽  
Vol 19 (6) ◽  
pp. 1516-1528 ◽  
Author(s):  
Anobel Tamrazi ◽  
Kathryn E. Carlson ◽  
Alice L. Rodriguez ◽  
John A. Katzenellenbogen
Keyword(s):  
Estrogen Receptor ◽  
Ligand Binding ◽  
Conformational Dynamics ◽  
Development Of Resistance ◽  
Coactivator Binding Inhibitors ◽  
High Concentrations ◽  
Vitro Model ◽  
And Function ◽  
Receptor Conformation

Abstract The direct regulation of gene transcription by nuclear receptors, such as the estrogen receptor (ER), involves not just ligand and DNA binding but the recruitment of coregulators. Typically, recruitment of p160 coactivator proteins to agonist-liganded ER is considered to be unidirectional, with ligand binding stabilizing an ER ligand binding domain (LBD) conformation that favors coactivator interaction. Using fluorophore-labeled ERα-LBDs, we present evidence for a pronounced stabilization of ER conformation that results from coactivator binding, manifest by decreased ER sensitivity to proteases and reduced conformational dynamics, as well as for the formation of a novel coactivator-stabilized (costabilized) receptor conformation, that can be conveniently monitored by the generation of an excimer emission from pyrene-labeled ERα-LBDs. This costabilized conformation may embody features required to support ER transcriptional activity. Different classes of coactivator proteins combine with estrogen agonists of different structure to elicit varying degrees of this receptor stabilization, and antagonists and coactivator binding inhibitors disfavor the costabilized conformation. Remarkably, high concentrations of coactivators engender this conformation even in apo- and antagonist-bound ERs (more so with selective ER modulators than with pure antagonists), providing an in vitro model for the development of resistance to hormone therapy in breast cancer.

scholarly journals Determining Aspergillus fumigatus transcription factor expression and function during invasion of the mammalian lung

2021 ◽  
Vol 17 (3) ◽  
pp. e1009235
Author(s):  
Hong Liu ◽  
Wenjie Xu ◽  
Vincent M. Bruno ◽  
Quynh T. Phan ◽  
Norma V. Solis ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Aspergillus Fumigatus ◽  
Transcriptional Profiling ◽  
Transcriptional Response ◽  
Gene Clusters ◽  
Transcription Factor Genes ◽  
And Function

To gain a better understanding of the transcriptional response of Aspergillus fumigatus during invasive pulmonary infection, we used a NanoString nCounter to assess the transcript levels of 467 A. fumigatus genes during growth in the lungs of immunosuppressed mice. These genes included ones known to respond to diverse environmental conditions and those encoding most transcription factors in the A. fumigatus genome. We found that invasive growth in vivo induces a unique transcriptional profile as the organism responds to nutrient limitation and attack by host phagocytes. This in vivo transcriptional response is largely mimicked by in vitro growth in Aspergillus minimal medium that is deficient in nitrogen, iron, and/or zinc. From the transcriptional profiling data, we selected 9 transcription factor genes that were either highly expressed or strongly up-regulated during in vivo growth. Deletion mutants were constructed for each of these genes and assessed for virulence in mice. Two transcription factor genes were found to be required for maximal virulence. One was rlmA, which is required for the organism to achieve maximal fungal burden in the lung. The other was sltA, which regulates of the expression of multiple secondary metabolite gene clusters and mycotoxin genes independently of laeA. Using deletion and overexpression mutants, we determined that the attenuated virulence of the ΔsltA mutant is due in part to decreased expression aspf1, which specifies a ribotoxin, but is not mediated by reduced expression of the fumigaclavine gene cluster or the fumagillin-pseruotin supercluster. Thus, in vivo transcriptional profiling focused on transcription factors genes provides a facile approach to identifying novel virulence regulators.

Ionic distribution in dopamine-stimulated NaCl fluid-secreting cockroach salivary glands

1983 ◽  
Vol 244 (2) ◽  
pp. R176-R186 ◽  
Author(s):  
B. L. Gupta ◽  
T. A. Hall
Keyword(s):  
Cell Membrane ◽  
Salivary Glands ◽  
Basal Cell ◽  
Periplaneta Americana ◽  
Ringer Solution ◽  
X Ray ◽  
Ionic Distribution ◽  
And Function ◽  
P Cells

The compound, racemose, innervated salivary glands of the cockroach Periplaneta americana closely resemble in structure and function the mammalian salivary glands (C.R. House, Biol. Rev. 55: 417-473, 1980). The quantitative distribution of Na, K, Cl, Ca, Mg, P, and S was investigated in the P-cells secreting isotonic NaCl and in duct lumens by using electron probe X-ray microanalysis of frozen-hydrated and frozen-dried cryosections. In the unstimulated glands in vitro the cells had (mmol/l cell-H2O) Na, 10; K, 110; Cl, 39 while the primary saliva had Na, 153; K, 4; Cl, 151. With 1 mumol dopamine in the bathing Ringer solution the P-cells had Na, 25; K, 177; Cl, 58 and the primary saliva, Na, 153; K, 26; Cl, 172. During passage through the ducts, the primary saliva was modified by an absorption of NaCl: more in unstimulated than in stimulated glands. It is proposed that the cells have a Na-K-ATPase both in the apical and basal cell membrane, as in vertebrate choroid plexus, and dopamine might increase the K and Na conductance of the basal cell membrane.

scholarly journals In Vitro Resistance of Staphylococcus aureus to Thrombin-Induced Platelet Microbicidal Protein Is Associated with Alterations in Cytoplasmic Membrane Fluidity

2000 ◽  
Vol 68 (6) ◽  
pp. 3548-3553 ◽  
Author(s):  
Arnold S. Bayer ◽  
Rajendra Prasad ◽  
Jyotsna Chandra ◽  
Anjni Koul ◽  
M. Smriti ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Membrane ◽  
Membrane Fluidity ◽  
Cytoplasmic Membrane ◽  
Membrane Lipids ◽  
Serial Passage ◽  
Membrane Structure And Function ◽  
Platelet Microbicidal Protein ◽  
And Function

ABSTRACT Platelet microbicidal proteins (PMPs) are small, cationic peptides which possess potent microbicidal activities against common bloodstream pathogens, such as Staphylococcus aureus. We previously showed that S. aureus strains exhibiting resistance to thrombin-induced PMP (tPMP-1) in vitro have an enhanced capacity to cause human and experimental endocarditis (T. Wu, M. R. Yeaman, and A. S. Bayer, Antimicrob. Agents Chemother. 38:729–732, 1994; A. S. Bayer et al., Antimicrob. Agents Chemother. 42:3169–3172, 1998; V. K. Dhawan et al., Infect. Immun. 65:3293–3299, 1997). However, the mechanisms mediating tPMP-1 resistance in S. aureus are not fully delineated. The S. aureus cell membrane appears to be a principal target for the action of tPMP-1. To gain insight into the basis of tPMP-1 resistance, we compared several parameters of membrane structure and function in three tPMP-1-resistant (tPMP-1r) strains and their genetically related, tPMP-1-susceptible (tPMP-1s) counterpart strains. The tPMP-1rstrains were derived by three distinct methods: transposon mutagenesis, serial passage in the presence of tPMP-1 in vitro, or carriage of a naturally occurring multiresistance plasmid (pSK1). All tPMP-1r strains were found to possess elevated levels of longer-chain, unsaturated membrane lipids, in comparison to their tPMP-1s counterparts. This was reflected in corresponding differences in cell membrane fluidity in the strain pairs, with tPMP-1r strains exhibiting significantly higher degrees of fluidity as assessed by fluorescence polarization. These data provide further support for the concept that specific alterations in the cytoplasmic membrane of S. aureus strains are associated with tPMP-1 resistance in vitro.

scholarly journals LXRα Phosphorylation in Cardiometabolic Disease: Insight From Mouse Models

Endocrinology ◽  
2020 ◽  
Vol 161 (7) ◽  
Author(s):  
Maud Voisin ◽  
Matthew C Gage ◽  
Natalia Becares ◽  
Elina Shrestha ◽  
Edward A Fisher ◽  
...  
Keyword(s):  
Nuclear Receptors ◽  
Posttranslational Modifications ◽  
Physiological Response ◽  
Metabolic Diseases ◽  
Cardiometabolic Disease ◽  
Nonalcoholic Fatty Liver ◽  
Environmental Signals ◽  
Powerful Means ◽  
And Function

Abstract Posttranslational modifications, such as phosphorylation, are a powerful means by which the activity and function of nuclear receptors such as LXRα can be altered. However, despite the established importance of nuclear receptors in maintaining metabolic homeostasis, our understanding of how phosphorylation affects metabolic diseases is limited. The physiological consequences of LXRα phosphorylation have, until recently, been studied only in vitro or nonspecifically in animal models by pharmacologically or genetically altering the enzymes enhancing or inhibiting these modifications. Here we review recent reports on the physiological consequences of modifying LXRα phosphorylation at serine 196 (S196) in cardiometabolic disease, including nonalcoholic fatty liver disease, atherosclerosis, and obesity. A unifying theme from these studies is that LXRα S196 phosphorylation rewires the LXR-modulated transcriptome, which in turn alters physiological response to environmental signals, and that this is largely distinct from the LXR-ligand–dependent action.

scholarly journals Estrogen receptor and aryl hydrocarbon receptor signaling pathways

2006 ◽  
Vol 4 (1) ◽  
pp. nrs.04016 ◽  
Author(s):  
Jason Matthews ◽  
Jan-Åke Gustafsson
Keyword(s):  
Estrogen Receptor ◽  
Transcription Factors ◽  
Estrogen Receptors ◽  
Aryl Hydrocarbon Receptor ◽  
Nuclear Receptors ◽  
Nuclear Receptor ◽  
Target Genes ◽  
Xenobiotic Metabolism ◽  
Positive Role ◽  
Aryl Hydrocarbon

Estrogen receptors (ERs) and the aryl hydrocarbon receptor (AhR) are ligand activated transcription factors and members of the nuclear receptor and bHLH-PAS superfamilies, respectively. AhR is involved in xenobiotic metabolism and in mediating the toxic effects of dioxin-like compounds. Crosstalk has been observed among AhR and nuclear receptors, but has been most well studied with respect to ER signaling. Activated AhR inhibits ER activity through a number of different mechanisms, whereas ERα has been reported to have a positive role in AhR signaling. Here we will discuss recent data revealing that dioxin bound AhR recruits ERα to AhR regulated genes. We will also consider the implications of ER recruitment to AhR target genes on ER and AhR signaling.

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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