Involvement of Ets, rel and Sp1-like proteins in lipopolysaccharide-mediated activation of the HIV-1 LTR in macrophages.
The HIV-1 promoter was used as a model to identify transcription factors involved in LPS-dependent transcription in RAW 264 murine macrophages. Expression plasmids for Ets-2 and PU.1 trans-activated the HIV-1 LTR and recombinant PU.1 and an Ets-2 DNA binding domain/GST fusion protein bound to the 5' kappa B site of the HIV-1 enhancer. Ets-2 mRNA was LPS-inducible in RAW 264 cells and LPS stimulated phosphorylation of threonine 72 residue within the Ets-2 pointed domain. Induction of Ets-2 and other LPS-responsive transcription factors was also observed upon addition of plasmid DNA, which complicates interpretation of transient transfections. The proximal promoter region, containing two Sp1 sites, was also LPS-responsive. We propose that the kappa B elements and the tandem Sp1 sites act as LPS response elements and that kappa B-mediated LPS action involves Ets and rel factors.
Sweet
M J
MJ
Department of Microbiology, University of Queensland, Brisbane, Australia.
Stacey
K J
KJ
Ross
I L
IL
Ostrowski
M C
MC
Hume
D A
DA
D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000494:pharmacology; D010957:Plasmids; D011401:Promoter Regions, Genetic; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins; D016329:Sp1 Transcription Factor / Q000494:pharmacology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D014157:Transcription Factors; D015533:Transcriptional Activation; D014162:Transfection; D000099232:Proto-Oncogene Protein Spi-1
D004247:DNA; D004268:DNA-Binding Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D016329:Sp1 Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; D000099232:Proto-Oncogene Protein Spi-1; C107465:ERF protein, human; C494070:Ets2 protein, mouse