Chimeric caspase molecules with potent cell killing activity in apoptosis-resistant cells

Cellular defects which prevent apoptotic cell death can result in the gener ation of hyperproliferative disorders and can prevent the effective treatme nt of such diseases. The majority of cellular defects which result, in apop tosis resistance lie upstream of caspase activation. We have described chim eric caspase molecules consisting of the prodomain of caspase-2 fused to th e amino terminus of caspase-3, and which are tagged at the carboxyl terminu s with green fluorescent protein (GFP) to allow direct visualisation of tra nsfected cells. Here we show that these chimeric caspase molecules possess potent, rapid cell-killing activity in cell lines which display a range of defects resulting in apoptosis resistance. (C) 2001 Academic Press.