Functional domains required for tat-induced transcriptional activation of the HIV-1 long terminal repeat.

AUTOR(ES)

Garcia, J A

RESUMO

The transcriptional regulation of the human immunodeficiency virus (HIV) type I involves the interaction of both viral and cellular proteins. The viral protein tat is important in increasing the amount of viral steady-state mRNA and may also play a role in regulating the translational efficiency of viral mRNA. To identify distinct functional domains of tat, oligonucleotide-directed mutagenesis of the tat gene was performed. Point mutations of cysteine residues in three of the four Cys-X-X-Cys sequences in the tat protein resulted in a marked decrease in transcriptional activation of the HIV long terminal repeat. Point mutations which altered the basic C-domain of the protein also resulted in decreases in transcriptional activity, as did a series of mutations that repositioned either the N or C termini of the protein. Conservative mutations of other amino acids in the cysteine-rich or basic regions and in a series of proline residues in the N terminus of the molecule resulted in minimal changes in tat activation. These results suggest that several domains of tat protein are involved in transcriptional activation with the cysteine-rich domain being required for complete activity of the tat protein.

Documentos Relacionados

• A transdominant tat mutant that inhibits tat-induced gene expression from the human immunodeficiency virus long terminal repeat.
• Functional roles for the TATA promoter and enhancers in basal and Tat-induced expression of the human immunodeficiency virus type 1 long terminal repeat.
• Cooperative inhibition of NF-kappa B and Tat-induced superactivation of human immunodeficiency virus type 1 long terminal repeat.
• Naturally occurring genotypes of the human immunodeficiency virus type 1 long terminal repeat display a wide range of basal and Tat-induced transcriptional activities.
• Characterization of a Major Histocompatibility Complex Class II X-Box-Binding Protein Enhancing Tat-Induced Transcription Directed by the Human Immunodeficiency Virus Type 1 Long Terminal Repeat