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Retinoid X receptor and c-erbA/ thyroid hormone receptor regulate erythroid cell growth and differentiation

Item Type:Article
Title:Retinoid X receptor and c-erbA/ thyroid hormone receptor regulate erythroid cell growth and differentiation
Creators Name:Bartunek, P. and Zenke, M.
Abstract:Nuclear receptors are important regulators of erythroid cell development. Here we investigated the impact of retinoid X receptor (RXR), retinoic acid receptor (RAR), and of the c-erbA/thyroid hormone (T3) receptor (c-erbA/TR) on growth and differentiation of erythroid cells using an in vitro culture system of stem cell factor-dependent erythroid progenitors. RXR, RAR, and c-erbA/TR-specific ligands were found to induce erythroid-specific gene expression and to accelerate erythroid differentiation in culture, with T3 being most effective. Furthermore, while ligand-activated c-erbA/TR accelerated differentiation, unliganded c-erbA/TR effectively blocked differentiation and supported sustained progenitor growth in culture. Thus, c-erbA/TR appears to act as a binary switch affecting erythroid cell fate: unliganded c-erbA/TR supports growth while ligand-activated c-erbA/TR induces differentiation. Additionally, to determine the impact of RXR for erythroid cell development, dominant interfering mutant RXRs, lacking the transcriptional activator functions AF-1 and AF-2, or AF-2 only, or the entire DNA-binding domain, were introduced into erythroid progenitor cells via recombinant retrovirus vectors and analyzed for RXR-specific effects. It was found that expression of wild-type RXR and of the RXR mutants devoid of AF-1 and/or AF-2 supported a transient outgrowth of erythroid cells. In marked contrast, expression of the dominant interfering deltaDNA-binding domain RXR, containing a deletion of the entire DNA-binding domain, was incompatible with erythroid cell growth in vitro, suggesting a pivotal role of RXR for erythroid cell development.
Keywords:Cell Differentiation, Cultured Cells, Erythroid Precursor Cells, Genetic Transcription, Genetic Vectors, Ligands, Retinoic Acid Receptors, Retinoid X Receptors, Retroviridae, Thyroid Hormone Receptors, Transcription Factors, Animals, Chickens
Source:Molecular Endocrinology
Publisher:Endocrine Society
Page Range:1269-1279
Date:September 1998
Official Publication:http://mend.endojournals.org/cgi/content/abstract/12/9/1269
PubMed:View item in PubMed

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