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 language | English (US) |
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Pages (from-to) | 1709-1720 |
Number of pages | 12 |
Journal | International Immunology |
Volume | 7 |
Issue number | 11 |
DOIs | |
State | Published - 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