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 |
|---|---|
| Pages (from-to) | 1709-1720 |
| Number of pages | 12 |
| Journal | International Immunology |
| Volume | 7 |
| Issue number | 11 |
| State | Published - Jan 1 1995 |
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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
Cite this
Pleiotropic effects of Bcl-2 on transcription factors in T cells : Potential role of NF-κB p50-p50 for the anti-apoptotic function of Bcl-2. / Ivanov, V. N.; Deng, G.; Podack, E. R.; Malek, Thomas.
In: International Immunology, Vol. 7, No. 11, 01.01.1995, p. 1709-1720.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Pleiotropic effects of Bcl-2 on transcription factors in T cells
T2 - Potential role of NF-κB p50-p50 for the anti-apoptotic function of Bcl-2
AU - Ivanov, V. N.
AU - Deng, G.
AU - Podack, E. R.
AU - Malek, Thomas
PY - 1995/1/1
Y1 - 1995/1/1
N2 - 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.
AB - 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.
KW - AP-1
KW - Apoptosis
KW - Dexamethasone
KW - IL-2
KW - NF-κB/Rel
KW - NF-AT
UR - http://www.scopus.com/inward/record.url?scp=0028827284&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028827284&partnerID=8YFLogxK
M3 - Article
C2 - 8580069
AN - SCOPUS:0028827284
VL - 7
SP - 1709
EP - 1720
JO - International Immunology
JF - International Immunology
SN - 0953-8178
IS - 11
ER -