Suppression of transcription factor NF-kappaB activity by Bcl-2 protein in NIH3T3 cells: implication of a novel NF-kappaB p50-Bcl-2 complex for the anti-apoptotic function of Bcl-2.
Bcl-2 can suppress apoptosis by controlling genes that encode proteins required for programmed cell death and by interference with peroxidative damage. Overexpression of Bcl-2 in NIH3T3 cells can prevent GSNO-induced (S-nitrosoglutathione-induced) apoptosis. The experimental results indicated that activation of NF-kappaB by GSNO is involved in inducing apoptosis. Surprisingly, we found that Bcl-2 delayed the release of IkB by formation of a Bcl-2-NF-kappaB complex (p50-p65-IkappaB) in the cytoplasm during cell apoptosis. Furthermore, a novel Bcl-2-p50 complex was found in the nucleus. These features were only observed in Bcl-2-transfected cells but not in the parental NIH3T3 cells. Overexpression of Bcl-2 suppressed the levels of c-myc, a target gene of NF-kappaB, and influenced the DNA-binding activity of NF-kappaB during GSNOinduced apoptosis. We suggest that the Bcl-2-p50 complex inhibits NF-kappaB DNA-binding activity by competing with the p65-p50 heterodimer for the DNA-binding site in the nucleus. Finally, it has been demonstrated that the anti-apoptotic potential of Bcl-2 may be attributed to its complexing with p50 in the nucleus that leads to blockage of nuclear gene expression.
Hour
T C
TC
Institute of Biochemistry, College of Medicine, National Taiwan University, Taipei.
Chen
L
L
Lin
J K
JK
D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D005786:Gene Expression Regulation; D051379:Mice; D016328:NF-kappa B / Q000235:genetics*; D052002:NF-kappa B p50 Subunit; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D014158:Transcription, Genetic
D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D019253:Proto-Oncogene Proteins c-bcl-2