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 propert ies of a conditional protein containing chicken c-Rel fused to the hor mone-binding domain of the human estrogen receptor. This chimeric c-Re lER protein causes estrogen-dependent, but otherwise c-Rel-specific, t ransformation of avian fibroblasts ill vitro. Our results demonstrate that c-RelER heterodimerizes with wild-type c-Rel and forms specific c omplexes with I kappa B-alpha. Estrogen causes translocation of c-RelE R 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 expr ession levels of c-RelER was stimulated by estrogen. In contrast, the addition of estrogen to cells with high c-RelER expression levels resu lted in inhibition of cytokinesis and the arrest of growth. The carbox y terminal transactivation domain of c-Rel was required for the induct ion of these effects since neither v-Rel nor c-Rel deletion mutants we re able to induce similar changes. Taken together, our results demonst rate that high levels of c-Rel expression can affect cell cycle contro l and/or cytokinesis. Furthermore, they also indicate that the biologi cal properties of c-Rel in cell growth and differentiation will potent ially differ depending on the level of expression.