Cell Cycle-Regulated Transcription by the Human Immunodeficiency Virus Type 1 Tat Transactivator

AUTOR(ES)

Kashanchi, Fatah

FONTE

American Society for Microbiology

RESUMO

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 G2 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 G1. This activation is TAR dependent and requires a functional Sp1 binding site. A second phase of transactivation by Tat is observed in G2 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 G2/M boundary. These studies link the HIV-1 Tat protein to cell cycle-specific biological functions.

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