Cell cycle-regulated transcription by the human immunodeficiency virus type 1 Tat transactivator.
Cyclin-dependent kinases are required for the Tat-dependent transition from abortive to productive elongation. Further, the human immunodeficiency virus type 1 (HIV-1) Vpr protein prevents proliferation of infected cells by arresting them in the G(2) phase of the cell cycle. These findings suggest that the life cycle of the virus may be integrally related to the cell cycle. We now demonstrate by in vitro transcription analysis that Tat-dependent transcription takes place in a cell cycle-dependent manner. Remarkably, Tat activates gene expression in two distinct stages of the cell cycle. Tat-dependent long terminal repeat activation is observed in G(1). This activation is TAR dependent and requires a functional Sp1 binding site. A second phase of transactivation by Tat is observed in G(2) and is TAR independent. This later phase of transcription is enhanced by a natural cell cycle blocker of HIV-1, vpr, which arrests infected cells at the G(2)/M boundary. These studies link the HIV-1 Tat protein to cell cycle-specific biological functions.
Kashanchi
F
F
Virus Tumor Biology Section, Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Agbottah
E T
ET
Pise-Masison
C A
CA
Mahieux
R
R
Duvall
J
J
Kumar
A
A
Brady
J N
JN
D002453:Cell Cycle; D002457:Cell Extracts; D000939:Epitopes / Q000235:genetics; D016193:G1 Phase; D016195:G2 Phase; D015967:Gene Expression Regulation, Viral; D015696:Gene Products, tat / Q000235:genetics / Q000378:metabolism*; D016336:Gene Products, vpr / Q000235:genetics / Q000378:metabolism; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics*; D006367:HeLa Cells; D006388:Hemagglutinins / Q000235:genetics; D006801:Humans; D016329:Sp1 Transcription Factor / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D054322:tat Gene Products, Human Immunodeficiency Virus; D054325:vpr Gene Products, Human Immunodeficiency Virus
D002457:Cell Extracts; D000939:Epitopes; D015696:Gene Products, tat; D016336:Gene Products, vpr; D006388:Hemagglutinins; D016329:Sp1 Transcription Factor; D054322:tat Gene Products, Human Immunodeficiency Virus; D054325:vpr Gene Products, Human Immunodeficiency Virus