Pleiotropic effects of Bcl-2 on transcription factors in T cells: potential role of NF-kappa B p50-p50 for the anti-apoptotic function of Bcl-2.
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-kappa B 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-kappa B levels, resulting in a decrease in RelA-p50 and an increase in NF-kappa B 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-kappa B/Rel levels raise the possibility that this family of transcription factors may play an important role in the regulation of apoptosis.
Ivanov
V N
VN
Department of Microbiology and Immunology, University of Miami School of Medicine, FL 33101, USA.
Deng
G
G
Podack
E R
ER
Malek
T R
TR
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D005822:Genetic Vectors / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D051841:Transcription Factor RelB; D014157:Transcription Factors / Q000187:drug effects* / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; C497594:Relb protein, mouse; D014157:Transcription Factors; D051841:Transcription Factor RelB; D003907:Dexamethasone