Role and regulation of Rel/NF-kappaB activity in anti-immunoglobulin-induced apoptosis in WEHI-231 B lymphoma cells.
In WEHI-231 cells, anti-immunoglobulin (anti-Ig) treatment leads to both a decrease in the DNA-binding activity of p50/c-Rel/p53 protein complexes and a transient enhancement in the DNA-binding activity of p50 homodimeric complexes. These cells subsequently undergo apoptosis. Because IkappaB-alpha plays a pivotal role in the regulation of Rel/NF-kappaB activity, we have characterized both the nature and kinetics of the expression of IkappaB-alpha following anti-Ig-induced apoptosis in WEHI-231 cells. Anti-Ig treatment of WEHI-231 cells decreased the steady-state level of IkappaB-alpha mRNA, but enhanced the stability of IkappaB-alpha, leading to an accumulation of IkappaB-alpha in both the cytosol and nucleus. Concomitant with the increase in IkappaB-alpha expression there was a gradual decline in the nuclear expression of c-Rel. Because c-Rel plays an important role in the survival of WEHI-231 cells, these results suggest that post-transcriptional regulation of IkappaB-alpha expression might play a role in the anti-Ig-induced apoptosis in WEHI-231 cells.
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Section of Molecular Genetics and Microbiology and the Institute for Cellular and Molecular Biology, The University of Texas at Austin, 78712-1095, USA.
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D000906:Antibodies / Q000494:pharmacology*; D017209:Apoptosis; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D019281:Dimerization; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020672:I-kappa B Proteins; D007700:Kinetics; D016393:Lymphoma, B-Cell; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D020569:Proto-Oncogene Proteins c-rel / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000906:Antibodies; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D020569:Proto-Oncogene Proteins c-rel; D000072000:NF-KappaB Inhibitor alpha