Caspases disrupt the nuclear-cytoplasmic barrier

During apoptosis, caspases, a family of proteases, disassemble a cell by cl eaving a set of proteins. Caspase-3 plays a major role in the disassembly o f the nucleus by processing several nuclear substrates. The question is how caspase-3, which is usually cytoplasmic, gains access to its nuclear targe ts. It was suggested that caspase-3 is actively transported to the nucleus through the nuclear pores. We found that caspase-9, which is activated earl ier than caspase-3, directly or indirectly inactivates nuclear transport an d increases the diffusion limit of the nuclear pores. This increase allows caspase-3 and other molecules that could not pass through the nuclear pores in living cells to enter or leave the nucleus during apoptosis by diffusio n. Hence, caspase-9 contributes to cell disassembly by disrupting the nucle ar-cytoplasmic barrier.