Induction of Apoptosis by Targeting the Microtubule Network: Using HIV Tat as a Model System
Abstract
Human immunodeficiency virus type 1 (HIV-l) is the etiological agent for the acquired immunodeficiency syndrome (AIDS). HIV-1 encodes a small trans-acting regulatory protein, Tat, which is absolutely essential for viral replication and is conserved in the genomes of all primate lentiviruses (Jones and Peterlin, 1994). A primary role of Tat is in regulating productive and processive transcription from the HIV-l long terminal repeat (LTR). The past decade has been a watershed for the biochemical analysis of the mechanism of Tat stimulation of HIV-l transcription. In addition to this HIV-l-speciflc activity, Tat has also been shown to impinge upon many cellular functions, some of which are consistent with the fact that Tat can be secreted by the HIV infected cells and act upon the neighboring bystander cells (Frankel and Pabo, 1988; Ensoli et al., 1990; Ensoli et al., 1993). Although the mechanisms for the secretion and uptake of Tat are mostly unclear, it is these unique properties that enable Tat to regulate cytokine gene expression and immune cell hyperactivation (Ott et a!., 1997), stimulate the growth of Kaposi's sarcoma cells (Ensoli et a!., 1990) and induce apoptosis of uninfected T cells (Li et a!,, 1995; Westendorp et a!., 1995; Bartz and Emerman, 1999). Apoptosis contributes to the massive depletion of CD4+ T cells and consequently to the loss of immune competence during HIV-l infection (Meyaard et al., 1992; Fauci, 1993). Although the mechanisms controlling apoptosis are likely to be multifactorial, Tat and a few other HIV-l gene products appear to contribute in part to the increased apoptosis associated with AIDS (Roshal et a!., 2001).
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2004
- Accession Number
- ADA428033
Entities
People
- Dan Chen
- Qiang Zhou
Organizations
- University of California, Berkeley