Tumour necrosis factor alpha and interleukin-1 beta induce specific subunits of NFKB to bind the HIV-1 enhancer: characterisation of transcription factors controlling human immunodeficiency virus type 1 gene expression in neural cells.
In human astrocytoma and neuroblastoma cell lines tumour necrosis factor alpha (TNF alpha) and interleukin 1 beta (IL-1 beta) induced NFKB and an additional KB-specific protein of approximately 80 K to bind the HIV-1 enhancer. One nucleoprotein complex contained prototypical NFKB comprising of p50 and p65 subunits and a second contained the p65 subunit and an 80 K factor, p80. Over a 24 hr period of cytokine stimulation the p50/p65 complex of NFKB was present in the nucleus whilst the second complex declined in abundance after two hours due to the decline of p80. In unstimulated cells, DNAse I footprinting revealed a previously unidentified octamer-like binding site in the negative regulatory element (NRE) of the HIV-1 long terminal repeat (LTR) which specifically bound protein factors present in human astrocytoma, neuroblastoma and murine oligodendroglioma cell lines. A second unique motif, also in the NRE, was observed with extracts from one human neuroblastoma cell line and a murine oligodendroglioma. Footprinting analysis also confirmed that Sp1, TATA, Site A and Site B motifs of the LTR were occupied by nuclear factors present in neural cells.
Swingler
S
S
Department of Biological Sciences, University of Warwick, Coventry, UK.
Morris
A
A
Easton
A
A
D001254:Astrocytoma; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004273:DNA, Neoplasm / Q000378:metabolism; D003850:Deoxyribonuclease I; D004742:Enhancer Elements, Genetic; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D009447:Neuroblastoma; D009474:Neurons / Q000378:metabolism; D009838:Oligodeoxyribonucleotides; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D004273:DNA, Neoplasm; D007375:Interleukin-1; D046911:Macromolecular Substances; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D003850:Deoxyribonuclease I