The Nuclear Receptor Field: A Historical Overview and Future Challenges

Mazaira, Gisela Ileana; Zgajnar, Nadia R.; Lotufo, Cecilia Maricel; Daneri-Becerra, Cristina; Sivils, Jeffrey C.; Soto, O. Bonilla; Cox, Marc B.; Galigniana, Mario D.

doi:10.11131/2018/101320

Cited by 75 publications

(57 citation statements)

References 154 publications

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“…NR can be referred to as the ligand-inducible transcription factors. For a review on NR refer to (Mazaira et al, 2018).…”

Section: Igfbp-3 and Nuclear Receptors (Nr) Functions As Transcriptiomentioning

confidence: 99%

“…The turning ON/OFF of downstream genes can in turn regulate different processes such as development, differentiation, metabolism, cell proliferation, and cell survival. The DNA sequences where the nuclear hormone receptors and their ligand complexes bind are referred to as the hormone response elements (HRE) (Mazaira et al, 2018).…”

Section: Igfbp-3 and Nuclear Receptors (Nr) Functions As Transcriptiomentioning

confidence: 99%

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Insulin-Like Growth Factor Binding Protein-3 (IGFBP-3): Unraveling the Role in Mediating IGF-Independent Effects Within the Cell

Shrivastav

Bhardwaj

Pathak

et al. 2020

Front. Cell Dev. Biol.

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“…NR can be referred to as the ligand-inducible transcription factors. For a review on NR refer to (Mazaira et al, 2018).…”

Section: Igfbp-3 and Nuclear Receptors (Nr) Functions As Transcriptiomentioning

confidence: 99%

Section: Igfbp-3 and Nuclear Receptors (Nr) Functions As Transcriptiomentioning

confidence: 99%

Insulin-Like Growth Factor Binding Protein-3 (IGFBP-3): Unraveling the Role in Mediating IGF-Independent Effects Within the Cell

Shrivastav

Bhardwaj

Pathak

et al. 2020

Front. Cell Dev. Biol.

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“…Although not exhaustive of all NR studies on epidermal keratinocytes, and clearly extending to many other tissues that are physiologically responsive to the diverse ligands of NRs, the above RAR, RXR and GR, MR studies suggest additional consideration of NR activation outside of their hallmark function as agonist-dependent transcription factors. NR function [15,16,56], including their transcriptional activation of target genes, is classically mapped through A/B -E/F subdomains (although F is not present in all receptors) from amino-to carboxyl-termini ends ( Figure 2).…”

Section: Nr Subdomains: Considering More Than Classic Structure-functionmentioning

confidence: 99%

Intrinsic Disorder in Nuclear Receptor Amino Termini: From Investigational Challenge to Therapeutic Opportunity

Shamilov

Aneskievich

2019

Nuclear Receptor Research

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Epidermal keratinocytes form an effective renewable barrier to surface assaults and desiccation of underlying tissues through a tightly controlled program of regeneration and terminal differentiation which is significantly impacted by the activity of several members of the nuclear receptor (NR) superfamily. As such, there is significant interest in physiological and pharmacological control of select NRs. NRs are usually considered quintessential examples of constrained structure-function relationships among protein families because of amino acid identity and sequence subserving physical requirements inherent to a relatively centrally-located DNA-binding domain and carboxyl-terminal ligand-recognition domain which together lead to agonistactivated gene expression. Nevertheless, across the superfamily the amino terminus of many NR is an often-critical contributor in degree of receptor-dependent transcriptional activity despite little in apparent sequence similarity that might be instructive in understanding this ability. By looking beyond shared strict amino acid sequence identity, a number of investigations are revealing the "unstructured"-function consequences of this disparity. Significant correlations between in silico and in vitro biophysical assessments are highlighting the shared trait of the unstructured nature or intrinsic disorder (ID) of NR amino termini and related functional consequences. Rather than the limited protein sequence variation-on-a-theme seen for zinc fingers (DNA binding) or a hydrophobic pocket (ligand binding), these amino-termini show sequence order diversity but often strikingly shared amino acid composition profiles not supporting a one-sequence-one-structure conformation. In this review, we look to integrate amino-termini ID reported in the literature, or predicted here, for select keratinocyte-expressed NR. As evidenced by success in drug targeting the amino-terminus of the androgen receptor, increased appreciation of amino-termini structure-or unstructure-might provide better understanding of NR function in general and possible future investigations on pharmacologic control over keratinocyte regeneration and/or differentiation.

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“…Rev-erbα (also called Nuclear Receptor Subfamily 1 Group D Member 1, NR1D1), an orphan nuclear receptor, encoded by Rev-erbα and belonged to the thyroid hormone receptor-like superfamily nuclear receptors [3], is part of the clock-keeping machinery [4] and plays an important role in regulating metabolism [5] and immunity [6]. It can physiologically modulate genes involved in lipid [7], bile acid [8] and glucose metabolism [9] in liver and adipose tissues.…”

Section: Introductionmentioning

confidence: 99%

Helicobacter pylori-induced Rev-erbα fosters gastric bacterial colonization by impairing host innate and adaptive defense

Zhuang

Mao

et al. 2020

Preprint

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Background: Helicobacter pylori (H. pylori) is a human pathogen that infects nearly half of the world’s population, however, the persistent colonization of H. pylori in gastric mucosa remains poorly understood. Nowadays it is believed that impairment of host defense of gastric epithelium induced by H. pylori plays key roles in H. pylori-associated pathology. The nuclear receptor Rev-erbα represents a powerful transcriptional repressor involved in host immunity. However, the regulation, function, and clinical relevance of Rev-erbα in H. pylori infection are presently unknown. Here we demonstrated a pro-colonization role of Rev-erbα in H. pylori infection.Results: Rev-erbα was increased in gastric mucosa of H. pylori-infected patients and mice. H. pylori induced gastric epithelial cells (GECs) to express Rev-erbα via the phosphorylated cagA that activated extracellular signal-regulated kinase (ERK) signaling pathway to mediate transcription factor nuclear factor kappa-B (NF-κB) directly binding to Rev-erbα promoter. Human gastric Rev-erbα expression correlated with H. pylori colonization, and mouse Rev-erbα from non-bone marrow-derived cells promoted gastric H. pylori burden. Importantly, H. pylori colonization was attenuated in Rev-erbα-/- mice and the mice with in vivo pharmacological inhibition of Rev-erbα. Mechanistically, Rev-erbα in GECs not only directly suppressed Reg3b and β-defensin-1 expression via binding to Reg3b and β-defensin-1 promoter respectively, which resulted in impaired bactericidal effects against H. pylori of these antibacterial proteins in vitro and in vivo; but also directly inhibited chemokine CCL21 expression via binding to CCL21 promoter, which led to decreased gastric influx of CD45+CD11c-Ly6G-CD11b+CD68- myeloid cells by CCL21-CCR7-dependent migration and, as a direct consequence, reduced bacterial clearing capacity of H. pylori-specific T helper type 1 (Th1) cell response. Conclusions: Overall, this study identifies a model involving Rev-erbα, which collectively ensures gastric bacterial persistence by suppressing host gene expression required for local innate and adaptive defense against H. pylori, and also highlight a pathological role and an immunosuppressive mechanism of Rev-erbα in persistent H. pylori infection.

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The Nuclear Receptor Field: A Historical Overview and Future Challenges

Cited by 75 publications

References 154 publications

Insulin-Like Growth Factor Binding Protein-3 (IGFBP-3): Unraveling the Role in Mediating IGF-Independent Effects Within the Cell

Insulin-Like Growth Factor Binding Protein-3 (IGFBP-3): Unraveling the Role in Mediating IGF-Independent Effects Within the Cell

Intrinsic Disorder in Nuclear Receptor Amino Termini: From Investigational Challenge to Therapeutic Opportunity

Helicobacter pylori-induced Rev-erbα fosters gastric bacterial colonization by impairing host innate and adaptive defense

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