NF-κB1 (p50) Homodimers Contribute to Transcription of the bcl-2 Oncogene

John F. Kurland, Reinhard Kodym, Michael D. Story, Kevin B. Spurgers, Timothy J. McDonnell, Raymond E. Meyn

Research output: Contribution to journalArticle

101 Scopus citations

Abstract

The bcl-2 proto-oncogene is frequently expressed in human cancer. Although bcl-2 was first cloned as the t(14;18) translocation breakpoint from human follicular B-cell lymphoma, it has become apparent that many cell types express bcl-2 because of transcriptional regulation. As such, several transcription factors have been demonstrated to activate expression of bcl-2, including NF-κB. We investigated the role of NFκB1 (p50) homodimers in the expression of Bcl-2 in two murine B-cell lymphoma cell lines: LY-as, an apoptosis-proficient line with low Bcl-2 protein expression and no nuclear NF-κB activity, and LY-ar, a nonapoptotic line with constitutive p50 homodimer activity and 30 times more Bcl-2 protein expression than LY-as. We found that nuclear p50 homodimer activity correlated with Bcl-2 expression in these cell types and identified several sites within the bcl-2 5′-flanking region that p50 was capable of binding. In vitro transcription revealed that recombinant p50 enhanced the production of run-off transcripts from the bcl-2 P1 promoter. Additional in vitro transcription experiments suggested the sites by which p50 afforded this effect. We conclude that the p50 homodimer is capable of transcriptional activation of the bcl-2 gene and suggest that its nuclear activity contributes to the expression of bcl-2 in LY-ar cells.

Original languageEnglish (US)
Pages (from-to)45380-45386
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number48
DOIs
StatePublished - Nov 30 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Kurland, J. F., Kodym, R., Story, M. D., Spurgers, K. B., McDonnell, T. J., & Meyn, R. E. (2001). NF-κB1 (p50) Homodimers Contribute to Transcription of the bcl-2 Oncogene. Journal of Biological Chemistry, 276(48), 45380-45386. https://doi.org/10.1074/jbc.M108294200