Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Erythroid differentiation leads to the production of red blood cells that contain a high level of hemoglobin. This level is mainly regulated by globin gene transcription during development and differentiation. Although numerous cis-acting sequences are involved in transcriptional activity of globin genes, combinations of three motifs, CCACC, SP1 and GATA represent the core elements of their regulatory sequences. These combinations are also found in promoters and/or enhancers of non-globin genes specifically expressed in the late stages of erythroid differentiation. The CCACC and SP1 sequences bind proteins that do not display erythrocytic specificity, and the GATA sequences bind a family of transacting factors recently cloned. The GATA family members are distinctive for a highly homologous DNA binding domain that exists in two zinc fingers reminiscent of those of the glucocorticoid receptor. None of the GATA family members displays only erythroid specificity, but gene disruption followed by rescue indicates that GATA-1 is necessary for terminal erythroid differentiation throughout development. The GATA/SP1 and GATA/CCACC associations are present in positive, negative or inducible regulatory sequences suggesting that other elements control the fine tuning of erythroid gene expression. NF-E2, which is a major transcriptional activator, members of the ets family which are implicated in the early stages of erythropoiesis and finally c-erbA which directly regulates a set of erythroid-specific genes are proteins that bind these latter regulatory motifs.
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PMID:Erythroid regulatory elements. 809 56

The v-erbA oncogene is a retrovirus-transduced and altered copy of a cellular gene (c-erbA-alpha) for a thyroid hormone receptor. In this paper we show that the v-erbA domains required for transcriptional activation in yeast and for oncogenic function in animal cells are closely congruent. We conclude that the behavior of the v-erbA protein as a transcriptional activator in yeast appears to closely reflect the same biochemical requirements that are necessary for v-erbA function in the neoplastic vertebrate cell. Intriguingly, parallel analyses of c-erbA-alpha and -beta demonstrated unexpected differences in the activities of the two thyroid hormone receptor isoforms in the yeast, perhaps reflecting different functions of these genes in vertebrates. Furthermore, results obtained by analysis of chimeric v-/c-erbA genes suggest that the basal and the hormone-induced transcriptional activity of the nuclear hormone receptors can be modulated independently by distinct structural features within the protein molecule.
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PMID:Functional domains of the v-erbA protein necessary for oncogenesis are required for transcriptional activation in Saccharomyces cerevisiae. 809 19

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.
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PMID:Retinoid X receptor and c-cerbA/thyroid hormone receptor regulate erythroid cell growth and differentiation. 973 97