Identification and characterization of nuclear factor κB binding sites in the murine bcl-x promoter

J. N. Glasgow, T. Wood, J. R. Perez-Polo

Research output: Contribution to journalArticlepeer-review

75 Scopus citations


Signal transduction pathways that mediate neuronal commitment to apoptosis involve the nuclear factor κB (NF-κB) transcription factor. Bcl-X(L) is a potent regulator of apoptosis in the CNS and is highly expressed in the developing and adult brain. We identified three putative NF-κB DNA binding sequences clustered up-stream of the brain-specific transcription start site in the upstream promoter region. Recombinant p50/p50 and NF-κB proteins from nuclear extracts bound to these sites as determined by electrophoretic mobility shift assay and biotin-oligonucleotide/streptavidin affinity assays. NF-κB overexpression, coupled with bcl-x promoter/reporter assays using a series of murine bcl-x promoter and deletion mutants, has identified the downstream 1.1 kb of the bcl-x promoter as necessary for basal promoter activity and induction by NF-κB. The mutagenic removal of NF-κB binding sites individually or in combination revealed altered response patterns to p49/p65 and p50/p65 overexpression. These results support the hypothesis that NF-κB can act to enhance Bcl-X(L) expression via highly selective interactions, where NF-κB binding and bcl-x promoter activation are dependent on both DNA binding site sequence and NF-κB subunit composition. Our data suggest that molecular events associated with NF-κB promote regulation of neuronal apoptosis in the developing or injured CNS.

Original languageEnglish (US)
Pages (from-to)1377-1389
Number of pages13
JournalJournal of neurochemistry
Issue number4
StatePublished - 2000


  • Apoptosis
  • Bcl-x
  • Nuclear factor κB
  • Promoter
  • Transcription

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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