The suppression of SH3BGRL is important for v-Rel-mediated transformation.
The v-rel oncogene is the most efficient transforming member of the Rel/NF-kappaB family of transcription factors. v-Rel induces avian and mammalian lymphoid cell tumors and transforms chicken embryo fibroblasts in culture by the aberrant regulation of genes under the control of Rel/NF-kappaB proteins. Here we report that the expression of SH3BGRL, a member of the SH3BGR (SH3 domain-binding glutamic acid-rich) family of proteins, is downregulated in v-Rel-expressing fibroblasts, lymphoid cells, and splenic tumor cells. Chromatin immunoprecipitation experiments demonstrated that v-Rel binds to the sh3bgrl promoter in transformed cells. Coexpression of SH3BGRL with v-Rel in primary splenic lymphocytes reduced the number of colonies formed by 76%. Mutations in the predicted SH3-binding domain of SH3BGRL abolished the suppressive effect on v-Rel transformation and resulted in colony numbers comparable to those formed by v-Rel alone. However, mutations in the predicted EVH1-binding domain of SH3BGRL only had a modest effect on suppression of v-Rel transformation. This study provides the first example of a gene that is downregulated in v-Rel-expressing cells that also plays a role in v-Rel transformation.
Majid
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Section of Molecular Genetics and Microbiology, Institute of Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712-1095, USA.
Liss
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You
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Bose
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic; D002642:Chick Embryo; D018076:DNA, Complementary; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D020572:Oncogene Proteins v-rel / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D018909:src Homology Domains
D018076:DNA, Complementary; D020572:Oncogene Proteins v-rel; D011506:Proteins; C113099:SH3BGRL protein, human