The suppression of SH3BGRL is important for v-Rel-mediated transformation

Oncogene. 2006 Feb 2;25(5):756-68. doi: 10.1038/sj.onc.1209107.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Transformation, Neoplastic*
  • Chick Embryo
  • DNA, Complementary
  • Electrophoretic Mobility Shift Assay
  • Humans
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Oncogene Proteins v-rel / physiology*
  • Promoter Regions, Genetic
  • Proteins / antagonists & inhibitors*
  • Proteins / genetics
  • Sequence Homology, Amino Acid
  • src Homology Domains


  • DNA, Complementary
  • Oncogene Proteins v-rel
  • Proteins
  • SH3BGRL protein, human