Jurkat cells respond to biotin deficiency with increased nuclear translocation of NF-kappaB, mediating cell survival.
Members of the NF-kappaB family of transcription factors cause transcriptional activation of anti-apoptotic genes. Here we determined whether survival of biotin-deficient cells is mediated by nuclear translocation of NF-kappaB. Human T (Jurkat) cells were cultured in biotin-deficient or biotin-supplemented media; nuclear translocation of NF-kappaB was stimulated with phytohemagglutinin and phorbol-12-myristate-13-acetate. Nuclear abundance of two members (p50 and p65) of the NF-kappaB family was greater in biotin-deficient compared to biotin-supplemented cells; this effect was mediated by phosphorylation of IkappaBalpha. The nuclear enrichment of p50 and p65 in biotin-deficient cells was associated with transcriptional activation of NF-kappaB-depedent genes such as the tumor suppressor gene p53 and the anti-apoptotic gene Bfl-1/A1. Biotin-deficient cells exhibited smaller activities of the apoptotic enzyme caspase-3 in response to treatment with tumor necrosis factor alpha, and decreased cell death in response to serum starvation compared to biotin-supplemented cells. These findings suggest that NF-kappaB mediates survival of biotin-deficient cells.
Department of Nutrition and Health Science, University of Nebraska at Lincoln, Lincoln, NE 68583-0806, USA.
Rocio
R
Rodriguez-Melendez
Lyndsay D
LD
Schwab
Janos
J
Zempleni
D017209:Apoptosis / Q000235:genetics; D001692:Biological Transport; D001710:Biotin / Q000008:administration & dosage / Q000172:deficiency*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D002470:Cell Survival; D005786:Gene Expression Regulation; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D019169:Jurkat Cells; D015778:Minor Histocompatibility Antigens; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D010835:Phytohemagglutinins / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
C096816:BCL2-related protein A1; D020672:I-kappa B Proteins; D015778:Minor Histocompatibility Antigens; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D010835:Phytohemagglutinins; D019253:Proto-Oncogene Proteins c-bcl-2; D000072000:NF-KappaB Inhibitor alpha; D001710:Biotin; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D013755:Tetradecanoylphorbol Acetate