Translational effects of peptide antagonists of Tat protein of human immunodeficiency virus type 1.
The Tat (trans-activator of transcription) regulatory protein of human immunodeficiency virus (HIV-1) acts by interacting with the TAR RNA domain of nascent viral transcripts and with cellular proteins to increase viral transcription. In Jurkat-derived HCLE-D36 cells, which are stably transfected with the chloramphenicol acetyltransferase (CAT) reporter gene expressed from the TAR-encoding long terminal repeat (LTR) of HIV-1, CAT protein expression is dependent on Tat. The Tat9-K-biotin peptide antagonist of Tat binds specifically to TAR RNA and competes with Tat for binding. In the cellular expression system, Tat9-K-biotin reduces Tat-dependent CAT expression. However, while the Tat antagonist greatly reduces CAT protein production and polysome association of CAT mRNA, it has little effect on CAT mRNA levels, suggesting that the antagonist works at the post-transcriptional level.
Choudhury
I
I
Wang
J
J
Stein
S
S
Rabson
A
A
Leibowitz
M J
MJ
D019380:Anti-HIV Agents / Q000494:pharmacology*; D001710:Biotin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002499:Centrifugation, Density Gradient; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D015696:Gene Products, tat / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology*; D017930:Genes, Reporter / Q000235:genetics; D016325:HIV Long Terminal Repeat / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D019169:Jurkat Cells; D010455:Peptides / Q000494:pharmacology; D011132:Polyribosomes / Q000187:drug effects / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus
D019380:Anti-HIV Agents; D015696:Gene Products, tat; D010455:Peptides; D012333:RNA, Messenger; C118267:Tat9-C-biotin; C118266:Tat9-K-biotin; D014764:Viral Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D001710:Biotin; D015500:Chloramphenicol O-Acetyltransferase