Involvement of 5'-flanking kB-like sites within bcl-x gene in silica-induced bcl-x expression.
Chen-F; Demers-LM; Vallyathan-V; Castranova-V; Shi-X
J Biol Chem 1999 Dec; 274(50):35591-35595
The present study investigated the involvement of the transcription factor NF-kappaB in the expression of an anti-apoptotic gene, bcl-x, using a murine macrophage cell line and peritoneal macrophages from both wild type p50(+/+)) and NF-kappaB p50 gene knockout (p50(-/-)) mice. Increased expression of Bcl-x protein was observed in native and silica-exposed p50(-/-) macrophages in which the NF-kappaB-containing complex was predominantly induced. Co-transfection experiment using a bcl-x promoter reporter construct and an expression vector for NF-kappaB p50 or p65 indicates that p65, but not p50, up-regulates the promoter activity of the bcl-x gene. DNA sequence analysis revealed that there are several kappaB-like sites within the 5'-flanking region of the bcl-x gene. Electrophoretic mobility shift assay suggested differences in binding of the NF-kappaB complexes to these putative NF-kappaB binding sites of the bcl-x gene.
Genetics; Carcinomas; DNA-damage; Cellular-reactions; In-vitro-studies
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Journal of Biological Chemistry