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

S M Majid1, A S Liss, M You

  • 1Section of Molecular Genetics and Microbiology, Institute of Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712-1095, USA.

Oncogene
|September 28, 2005
PubMed

Insights

The v-Rel oncogene downregulates SH3BGRL, a protein involved in cell transformation. Suppressing v-Rel

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • The v-Rel oncogene, a potent member of the Rel/NF-kappaB transcription factor family, drives lymphoid cell tumors and transforms fibroblasts.
  • Aberrant gene regulation by Rel/NF-kappaB proteins underlies v-Rel's oncogenic activity.

Purpose of the Study:

  • To investigate the role of SH3BGRL (SH3 domain-binding glutamic acid-rich) in v-Rel-mediated cell transformation.
  • To identify genes downregulated by v-Rel that are functionally involved in its oncogenic effects.

Main Methods:

  • Quantitative analysis of SH3BGRL expression in v-Rel-expressing cells (fibroblasts, lymphoid cells, splenic tumors).
  • Chromatin immunoprecipitation (ChIP) to assess v-Rel binding to the sh3bgrl promoter.
  • Coexpression studies of SH3BGRL and v-Rel in primary splenic lymphocytes, including mutational analysis of SH3BGRL domains.

Main Results:

  • SH3BGRL expression is significantly downregulated in v-Rel-transformed cells.
  • v-Rel directly binds to the sh3bgrl promoter in transformed cells.
  • Overexpression of SH3BGRL suppresses v-Rel-induced transformation by 76%; mutations in the SH3-binding domain abolish this suppression, while EVH1-binding domain mutations have a minor effect.

Conclusions:

  • SH3BGRL is a novel tumor suppressor downregulated by v-Rel.
  • The SH3-binding domain of SH3BGRL is critical for its suppressive role in v-Rel transformation.
  • This study identifies a new mechanism of oncogenesis involving v-Rel-mediated downregulation of a tumor suppressor gene.

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