Abstract
The net distribution of eukaryotic transcription factors between the cytoplasm and the nucleus provides an effective mechanism for controlling gene expression. We have utilized cis-acting signals for both nuclear import and nuclear export to experimentally manipulate the distribution of the v-Rel oncoprotein between the nucleus and the cytoplasm. The respective abilities of the v-Rel oncoprotein to localize to the nucleus in chicken embryo fibroblasts, to activate κB-dependent transcription in yeast, and to transform avian lymphoid cells were each markedly reduced by the fusion of a cis-acting nuclear export signal onto v-Rel. Our results demonstrate that a threshold nuclear function of v-Rel is required for manifestation of its oncogenic properties. In contrast, while increased expression of the avian IκB-α protein was able to prevent nuclear localization of v-Rel in chicken embryo fibroblasts, coexpression of IκB-α with v-Rel in the target cell for v-Rel mediated transformation did not reduce the ability of v-Rel to transform avian lymphoid cells or alter the distribution of v-Rel between the nucleus and the cytoplasm in v-Rel-transformed cells. Our results suggest that the ability of IκB-α to inhibit nuclear localization of v-Rel is affected by cell-type specific differences between fibroblasts and lymphoid cells.
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Sachdev, S., Diehl, J., McKinsey, T. et al. A threshold nuclear level of the v-Rel oncoprotein is required for transformation of avian lymphocytes. Oncogene 14, 2585–2594 (1997). https://doi.org/10.1038/sj.onc.1201108
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DOI: https://doi.org/10.1038/sj.onc.1201108
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