Suppression of transcription factor NF-κB activity by Bcl-2 protein in NIH3T3 cells: implication of a novel NF-κB p50-Bcl-2 complex for the anti-apoptotic function of Bcl-2

• Published in: European journal of cell biology 2000-02, Vol.79 (2), p.121-129
• Main Authors: Hour, Tzyh-Chyuan, Chen, Linda, Lin, Jen-Kun
• Format: Article
• Language: English
• Subjects: apoptosis; Bcl-2; NF-κB; NIH3T3 cells; S-nitrosoglutathione
• ISSN: 0171-9335; 1618-1298
• DOI: 10.1078/S0171-9335(04)70014-X

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-κB by GSNO is involved in inducing apoptosis. Surprisingly, we found that Bcl-2 delayed the release of IκB by formation of a Bcl-2-NF-κB complex (p50-p65-IκB) 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-κB, and influenced the DNA-binding activity of NF-κB during GSNO-induced apoptosis. We suggest that the Bcl-2-p50 complex inhibits NF-κB 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.