Transcription factor PRDII-BF1 activates human immunodeficiency virus type 1 gene expression.
Gene expression of human immunodeficiency virus (HIV) is modulated by both cellular transcription factors, which bind to cis-acting regulatory elements in the HIV-1 long terminal repeat (LTR) and the viral transactivator, tat. The enhancer element in the HIV-1 LTR which extends from -103 to -82 is critical for gene expression. This region contains two identical 10-bp direct repeats which serve as binding sites for members of the NF-kappa B family of transcription factors. However, several other cellular transcription factors, including a group of zinc finger DNA-binding proteins, also bind to NF-kappa B and related motifs. A member of this family of transcription factors, designated PRDII-BF1 or MBP-1, is a 300-kDa cellular protein which contains two widely separated zinc finger DNA binding domains. Each of these binding domains is capable of binding to NF-kappa B or related recognition motifs. Since no functional role for this protein has been demonstrated in the regulation of viral and cellular promoters, we began studies to determine whether PRDII-BF1 could modulate HIV-1 gene expression. DNase I footprinting of the HIV-1 LTR indicated that PRDII-BF1 bound to both NF-kappa B and TAR transactivation response DNA elements. Both in vitro translation and vaccinia virus expression of PRDII-BF1 cDNA resulted in the synthesis of the full-length 300-kDa PRDII-BF1 protein. Transfection experiments, using both eucaryotic expression vectors and antisense constructs, indicated that PRDII-BF1 activated HIV-1 gene expression in both the presence and absence of tat. These results are consistent with a role for PRDII-BF1 in activating HIV-1 gene expression.
Seeler
J S
JS
Department of Medicine, Southwestern Medical School, Dallas, Texas 75235.
Muchardt
C
C
Suessle
A
A
Gaynor
R B
RB
D001483:Base Sequence; D003001:Cloning, Molecular; D016373:DNA, Antisense; D004268:DNA-Binding Proteins / Q000494:pharmacology*; D004742:Enhancer Elements, Genetic / Q000235:genetics; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D017930:Genes, Reporter; D016325:HIV Long Terminal Repeat / Q000235:genetics; D015497:HIV-1 / Q000235:genetics*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D015183:Restriction Mapping; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000187:drug effects*; D015533:Transcriptional Activation; D016335:Zinc Fingers
D016373:DNA, Antisense; D004268:DNA-Binding Proteins; C063232:HIVEP1 protein, human; D016328:NF-kappa B; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors