title: A threshold nuclear level of the v-Rel oncoprotein is required for transformation of avian lymphocytes.
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 kappaB-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 IkappaB-alpha protein was able to prevent nuclear localization of v-Rel in chicken embryo fibroblasts, coexpression of IkappaB-alpha 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 IkappaB-alpha to inhibit nuclear localization of v-Rel is affected by cell-type specific differences between fibroblasts and lymphoid cells.
authors.affiliation: Department of Biochemistry, University of Missouri-Columbia, 65212, USA.
authors.forename: S
authors.initials: S
authors.lastname: Sachdev
authors.forename: J A
authors.initials: JA
authors.lastname: Diehl
authors.forename: T A
authors.initials: TA
authors.lastname: McKinsey
authors.forename: A
authors.initials: A
authors.lastname: Hans
authors.forename: M
authors.initials: M
authors.lastname: Hannink
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002471:Cell Transformation, Neoplastic; D002642:Chick Embryo; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology; D020672:I-kappa B Proteins; D008214:Lymphocytes / Q000378:metabolism / Q000502:physiology*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D020572:Oncogene Proteins v-rel; D015682:Retroviridae Proteins, Oncogenic / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; D020572:Oncogene Proteins v-rel; D015682:Retroviridae Proteins, Oncogenic; D014157:Transcription Factors; D000072000:NF-KappaB Inhibitor alpha