TY - JOUR
T1 - Regulation of the HIV1 long terminal repeat by mutant heat shock factor
AU - Ignatenko, Natalia A.
AU - Gerner, Eugene W.
N1 - Funding Information:
We thank Dr. Richard Voellmy, University of Miami, for his generous gift of the HSF1 (+) plasmid and for critical review of the manuscript. The authors also thank David Stringer in our department for editing the manuscript. Supported by Grants CA23074 and CA72008 from the USPHS/NCI and Contract 9829 from the Arizona Disease Control Research Commission.
PY - 2003/8/1
Y1 - 2003/8/1
N2 - 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-κB, 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.
AB - 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-κB, 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.
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U2 - 10.1016/S0014-4827(03)00186-1
DO - 10.1016/S0014-4827(03)00186-1
M3 - Article
C2 - 12878154
AN - SCOPUS:0038149055
SN - 0014-4827
VL - 288
SP - 1
EP - 8
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 1
ER -