Abstract
The v-rel oncogene is the most efficient transforming member of the Rel/NF-κB 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-κB 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.
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Acknowledgements
We thank William Bargmann, Radmila Hrdlicková, Jarmila Kralova, Jiri Nehyba, and Emin Ulug for technical advice and critical reading of the manuscript. This work was supported by Public Health Service grant CA33192 from the National Cancer Institute.
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Majid, S., Liss, A., You, M. et al. The suppression of SH3BGRL is important for v-Rel-mediated transformation. Oncogene 25, 756–768 (2006). https://doi.org/10.1038/sj.onc.1209107
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DOI: https://doi.org/10.1038/sj.onc.1209107
Keywords
- v-Rel
- NF-κB
- SH3BGRL
- SH3BGR
- transformation
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