Alterations in the nucleocytoplasmic transport in apoptosis: Caspases lead the way

Abstract

Apoptosis is a mode of regulated cell death that is indispensable for the morphogenesis, development and homeostasis of multicellular organisms. Caspases are cysteine-dependent aspartate-specific proteases, which function as initiators and executors of apoptosis. Caspases are cytosolic proteins that can cleave substrates located in different intracellular compartments during apoptosis. Many years ago, the involvement of caspases in the regulation of nuclear changes, a hallmark of apoptosis, was documented. Accumulated data suggest that apoptosis-associated alterations in nucleocytoplasmic transport are also linked to caspase activity. Here, we aim to discuss the current state of knowledge regarding this process. Particular attention will be focused on caspase nuclear entry and their functions in the demolition of the nucleus upon apoptotic stimuli.

Figure 1

Caspases target components of the nucleocytoplasmic transport and proteins maintaining nuclear integrity. Caspases have been found to cleave at least 8 of 30 proteins of the NPC and importins (Table 1), which leads to the destabilization of active transport. Caspases are depicted as a pair of scissors

Figure 2

Caspases indirectly promote the demolition of the nucleus during apoptosis. The caspase‐dependent cleavage of a target can lead to its inactivation (red line) or the formation of an active product (green line). The phosphorylation of a target protein (dashed line) by caspase‐activated kinases results in chromatin condensation and the transcription of pro‐apoptotic genes