Identification of a novel human zinc finger protein that specifically interacts with the activation domain of lentiviral Tat proteins.
Transcriptional activation of HIV-1 gene expression by the viral Tat protein requires the interaction of a cellular cofactor with the Tat activation domain. This domain has been shown to consist of the cysteine-rich and core motifs of HIV-1 Tat and is functionally conserved in the distantly related Tat proteins of HIV-2 and EIAV. Using the yeast two-hybrid system, we have identified a novel human gene product, termed HT2A, that specifically and precisely binds to the activation domain of HIV-1 Tat and that can also interact with the HIV-2 and EIAV Tat proteins in vivo. We present data further demonstrating that the interaction between the activation domain of HIV-1 Tat and the HT2A protein can be readily detected in the mammalian cell nucleus. Sequence analysis demonstrates that HT2A is a novel member of the C3HC4 or ring finger family of zinc finger proteins that includes several known oncogenes and transcription factors. Overall, these data suggest that HT2A may play a significant role in mediating the biological activity of the HIV-1 Tat protein in vivo.
Fridell
R A
RA
Howard Hughes Medical Institute, Durham, North Carolina, USA.
Harding
L S
LS
Bogerd
H P
HP
Cullen
B R
BR
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D015500:Chloramphenicol O-Acetyltransferase / Q000032:analysis / Q000096:biosynthesis; D002522:Chlorocebus aethiops; D018076:DNA, Complementary; D015696:Gene Products, tat / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D015498:HIV-2 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007668:Kidney; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000032:analysis / Q000096:biosynthesis; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; D016335:Zinc Fingers / Q000502:physiology*; D054322:tat Gene Products, Human Immunodeficiency Virus
D018076:DNA, Complementary; D015696:Gene Products, tat; D011994:Recombinant Proteins; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D015500:Chloramphenicol O-Acetyltransferase; C094027:TRIM32 protein, human; D044767:Ubiquitin-Protein Ligases