Nuclear receptors (NRs), are a wide family of ligand-regulated transcription factors sharing a common modular structure composed by an N-terminal domain and a ligand-binding domain connected by a short hinge linker to a DNA-binding domain. NRs are involved in many physiological processes, including metabolism, reproduction and development. Most of them respond to small lipophilic ligands, such as steroids, retinoids, and phospholipids, which act as conformational switches. Some NRs are still “orphan” and the search for their ligands is still ongoing. Upon DNA binding, NRs can act both as transcriptional activators or repressors of their target genes. Theoretically, the possibility to modulate NRs activity with small molecules makes them ideal therapeutic targets, although the complexity of their signaling makes drug design challenging. In this review, we discuss the role of NRs in erythropoiesis, in both homeostatic and stress conditions. This knowledge is important in view of modulating red blood cells production in disease conditions, such as anemias, and for the expansion of erythroid cells in culture for research purposes and for reaching the long-term goal of cultured blood for transfusion.

Pastori, V., Pozzi, S., Labedz, A., Ahmed, S., Ronchi, A. (2022). Role of Nuclear Receptors in Controlling Erythropoiesis. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 23(5) [10.3390/ijms23052800].

Role of Nuclear Receptors in Controlling Erythropoiesis

Pastori V.;Labedz A.;Ahmed S.;Ronchi A. E.
2022

Abstract

Nuclear receptors (NRs), are a wide family of ligand-regulated transcription factors sharing a common modular structure composed by an N-terminal domain and a ligand-binding domain connected by a short hinge linker to a DNA-binding domain. NRs are involved in many physiological processes, including metabolism, reproduction and development. Most of them respond to small lipophilic ligands, such as steroids, retinoids, and phospholipids, which act as conformational switches. Some NRs are still “orphan” and the search for their ligands is still ongoing. Upon DNA binding, NRs can act both as transcriptional activators or repressors of their target genes. Theoretically, the possibility to modulate NRs activity with small molecules makes them ideal therapeutic targets, although the complexity of their signaling makes drug design challenging. In this review, we discuss the role of NRs in erythropoiesis, in both homeostatic and stress conditions. This knowledge is important in view of modulating red blood cells production in disease conditions, such as anemias, and for the expansion of erythroid cells in culture for research purposes and for reaching the long-term goal of cultured blood for transfusion.
Articolo in rivista - Review Essay
Erythropoiesis; Globins genes expression during development; Nuclear receptors; Stress erythropoiesis;
English
27-feb-2022
2022
23
5
2800
open
Pastori, V., Pozzi, S., Labedz, A., Ahmed, S., Ronchi, A. (2022). Role of Nuclear Receptors in Controlling Erythropoiesis. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 23(5) [10.3390/ijms23052800].
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