MODEL FOR APOPTOSIS VS. NECROSIS
The expression of HIV PR in transfected cells, therefore, can cause death through apoptosis or necrosis. This seeming paradox may be reconciled by observations that stimuli other than PR may, in different contexts, lead to apoptosis or necrosis.
For example, caspase inhibitors can switch cell death from apoptosis phenotype to necrosis.33 Another example shows two functional domains of FADD point cell death signals to different directions — to DED induction of apoptosis through interaction with procaspase-8 and death domain (DD) activation resulting in necrosis via binding RIP.34 Therefore, it is possible that HIV PR induces cell death either through apoptosis or necrosis, potentially depending on PR expression levels. Such a model is reminiscent of lysosomal proteases, for example, cathepsin B. When small amounts of cathepsin B are in the cytosol, caspases are activated, inducing apoptosis, but when larger amounts are released from ruptured lysosomes, the cell death phenotype resembles necrosis.35
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