A chicken c-Rel-estrogen receptor chimeric protein shows conditional nuclear localization, DNA binding, transformation and transcriptional activation.
In this report, we characterize the biological and biochemical properties of a conditional protein containing chicken c-Rel fused to the hormone-binding domain of the human estrogen receptor. This chimeric c-RelER protein causes estrogen-dependent, but otherwise c-Rel-specific, transformation of avian fibroblasts in vitro. Our results demonstrate that c-RelER heterodimerizes with wild-type c-Rel and forms specific complexes with IkappaB-alpha. Estrogen causes translocation of c-RelER to the nucleus and stabilizes its binding to DNA. Hormone-activated c-RelER induces transcription of at least four cellular genes that are constitutively active in wild-type c-Rel-transformed fibroblasts. Two distinct cell populations were examined that differed with respect to their growth phenotypes. The growth of fibroblasts with moderate expression levels of c-RelER was stimulated by estrogen. In contrast, the addition of estrogen to cells with high cRelER expression levels resulted in inhibition of cytokinesis and the arrest of growth. The carboxy terminal transactivation domain of c-Rel was required for the induction of these effects since neither v-Rel nor c-Rel deletion mutants were able to induce similar changes. Taken together, our results demonstrate that high levels of c-Rel expression can affect cell cycle control and/or cytokinesis. Furthermore, they also indicate that the biological properties of c-Rel in cell growth and differentiation will potentially differ depending on the level of expression.
Department of Microbiology State University of New York at Stony Brook, 11794, USA.
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Zurovec
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Petrenko
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Roll
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Enrietto
D000818:Animals; D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic; D002642:Chick Embryo; D002999:Clone Cells; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D010641:Phenotype; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020569:Proto-Oncogene Proteins c-rel; D011784:Quail; D011960:Receptors, Estrogen / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D004247:DNA