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

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

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-_KB 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-_KB levels, resulting in a decrease in RelA-p50 and an increase In NF-_KB 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-_KB/ROI levels raise the possibility that this family of transcription factors may play an important role in the regulation of apoptosis.


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International Immunology

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Academic Units
Center for Radiological Research
Oxford University Press
Published Here
September 11, 2015