Regulation of the HIV1 long terminal repeat by mutant heat shock factor.
Heat shock is a known transcriptional activator of human immunodeficiency virus type 1 (HIV1) long terminal repeat (LTR). However, HIV1 LTR suppression can occur under hyperthermic conditions. To investigate this phenomenon, a series of HIV1 LTR deletion luciferase constructs were generated and tested in cell culture in combination with a mutant heat shock factor 1 (HSF1+), which is transcriptionally active in the absence of heat stress. HSF1+ suppressed the activity of a minimal HIV1 LTR promoter, which contained NF-kappaB, Sp1, and tat consensus sequences. Electromobility shift assays showed nuclear protein-DNA complex formation with a Sp1 consensus sequence. Immunoprecipitation of nuclear extracts with Sp1 antibody did not affect nuclear protein-Sp1 oligonucleotide complex formation. In contrast, no complexes were formed with the Sp1 consensus sequence when the HSF protein was immunoprecipitated. These experiments indicate that modified heat shock factor can suppress HIV1 promoter activity by a mechanism involving interaction with Sp1 elements in the HIV1 promoter. The ability of HSF1+ to suppress HIV1 promoter activity suggests that HSF1+ could serve as a tool for the treatment of AIDS.
Ignatenko
Natalia A
NA
Department of Radiation Oncology/Cancer Biology Section, Arizona Cancer Center, The University of Arizona, 1515 N. Campbell Avenue, Tucson, AZ 85724, USA. nignatenko@azcc.arizona.edu
Gerner
Eugene W
EW
D020816:Amino Acid Motifs; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D015967:Gene Expression Regulation, Viral; D017930:Genes, Reporter; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D000076249:Heat Shock Transcription Factors; D006358:Hot Temperature; D006801:Humans; D009154:Mutation; D011401:Promoter Regions, Genetic; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D016329:Sp1 Transcription Factor; D014157:Transcription Factors