CELL CYCLE ARREST AND APOPTOSIS

摘要

The HIV-1 accessory gene vpr encodes a conserved 96-amino acid protein that is necessary and sufficient for the HIV-­1 -induced block of cellular proliferation and induction of apoptosis. Expression of vpr in CD4<SUP>+</SUP> lymphocytes results in G2 arrest, followed by apoptosis. ATR, as a cellular factor that mediates Vpr-induced cell cycle arrest, is required for activation of the Breast Cancer-Associated Protein-I (BRCAI). In addition, the Growth Arrest and DNA Damage protein (GADD45) is upregulated by Vpr in an ATR-dependent manner. Posttranscriptional silencing of either ATR or GADD45 leads to nearly complete suppression of the pro-apoptotic and/or cell cycle arrest effect of Vpr.