An updated evolutionary study of the nuclear receptor protein family

Abstract

The nuclear receptor (NR) superfamily is comprised of transcription factors that are ligand-activated in their majority and play a pivotal role in biological functions that are essential for life, such as metabolism and homeostasis. Following activation, they undertake the regulation of the transcription of their target genes with the help of co-regulator proteins, rendering them very promising pharmacological targets. In total, 59 NRs have been discovered in several species of the Animalia kingdom, 20 of which are still orphan receptors. The present study aimed to further enlighten the evolutionary scenario that reveals the association between members of the NR superfamily. An updated evolutionary analysis was performed for the NR protein superfamily with the aim of clustering all the NRs, and discovering conserved regions and motifs that play major roles in their signaling pathway; the mechanisms of action were also investigated. The findings of the present study demonstrate a clear separation of the NR family in three majors monophyletic branches, the steroid hormone-related, the thyroid hormone-related and the retinoid X receptor-related clusters, from which, through evolution, may correspond to three ancestral NRs that were differentiated from a common ancestral NR.

An updated evolutionary and structural study of TBK1 reveals highly conserved motifs as potential pharmacological targets in neurodegenerative diseases

“…The aligned TBK1 sequences were subsequently studied carefully in Jalview for the identification of conserved regions (39). The commentary section of Jalview, which presents the amino-acid conservation using logos and histograms, was further observed to uncover novel motifs (40). Lastly, phylogenetic analysis was performed with MATLAB Bioinformatics Toolbox, utilizing the Unweighted Pair-Group Method (UPGMA) (41).…”

“…The resulting dataset includes naturally occurring TBK1 mutations in the following domains: kinase domain, ULD domain, CCD1 and CCD2 domain. Based on the generated list, mutations were identified and marked on the consensus sequence in the study’s multiple sequence alignment (40).…”

A genomic study of the Japanese population focusing on the glucocorticoid receptor interactome highlights distinct genetic characteristics associated with stress response

“…Thus, a research focus on GR can illuminate various aspects of the stress response system. GR and ΜR are transcription factors that belong to the superfamily of nuclear receptors (6,7,9,18). Nuclear receptors are ligand-dependent and regulate gene expression through DNA binding (19).…”

“…ACTH is then released into the circulation, which in turn stimulates glucocorticoid production and release from the adrenal cortex (4). Glucocorticoids, cortisol in humans and corticosterone in rodents are steroid hormones synthesized and released by the adrenal glands in a circadian manner (5)(6)(7). Cortisol can control CRH, AVP, and ACTH secretion in order to avoid prolonged HPA activity through sensitive negative feedback (8,9).…”

“…GR and MR are transcription factors that belong to the superfamily of nuclear receptors (6, 7, 9, 18). Nuclear receptors are ligand-dependent and regulate gene expression through DNA binding (19).…”