Cell cycle arrest and apoptosis

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Reexamination Certificate

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C424S093100

Reexamination Certificate

active

07973018

ABSTRACT:
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+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-1 (BRCA1). 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.

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