Pleiotropic effects of Bcl-2 on transcription factors in T cells: Potential role of NF-kB p50-p50 for the anti-apoptotic function of Bcl-2

Vladimir N. Ivanov, Ge Deng, Eckhard R. Podack, Thomas R. Malek

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Bcl-2 functions to repress apoptosis by regulation of genes which encode proteins required for programmed cell death and by interference with peroxidative damage. We investigated the interrelationship between expression of bcl-2 and regulation of transcription factor DNA binding activities in the 2B4 T cell hybridoma and IL-2-dependent CTLL T cell line. Over-expression of bcl-2 in 2B4 resulted in enhanced basal levels of activator protein (AP)-1, octamer binding factor (Oct)-1, lymphoid enhancer binding factor (LEF)-1, RelA-p50 and NF-κB p50-p50 DNA binding activities. After apoptotic signaling, down-regulation of AP-1, NF-AT and Oct-1 binding activities was observed in control 2B4 and CTLL, whereas suboptimal, but higher, levels of these transcription factors were found in bcl-2-transfected cells, potentially promoting cell survival. Furthermore, after apoptotic signaling, expression of bcl-2 led to differential changes of NF-κB levels, resulting in a decrease in RelA-p50 and an increase in NF-κB p50-p50, altering the ratio of these DNA binding activities such that now p50-p50 markedly predominated in both 2B4-Bcl-2 and CTLL-Bcl-2. Apoptotic signaling in the presence or absence of Bcl-2 resulted in induction of the RelB-p50 heterodimer in 2B4. The changes in NF-κB/Rel levels raise the possibility that this family of transcription factors may play an important role in the regulation of apoptosis.

Original languageEnglish (US)
Pages (from-to)1709-1720
Number of pages12
JournalInternational Immunology
Volume7
Issue number11
DOIs
StatePublished - Nov 1995

Keywords

  • AP-1
  • Apoptosis
  • Dexamethasone
  • IL-2
  • NF-κB/Rel
  • NF-AT

ASJC Scopus subject areas

  • Immunology
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Public Health, Environmental and Occupational Health
  • Neuropsychology and Physiological Psychology
  • Transplantation

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