procaspase7

Procaspase-7 is the zymogen form of caspase-7, a cysteine protease of the executioner subgroup of the caspase family. Caspases are proteolytic enzymes that cleave substrates after aspartate residues to execute apoptosis and participate in other cellular processes. Procaspase-7 is activated through proteolytic processing to form the active enzyme complex that mediates downstream apoptotic events.

Activation and maturation: In response to apoptotic signals, initiator caspases such as caspase-9 (via the intrinsic pathway) or caspase-8 (via the extrinsic pathway) cleave procaspase-7 to generate the active enzyme, which consists of two large and two small subunits that assemble into an active heterotetramer. Granzyme B, delivered by cytotoxic T cells and natural killer cells, can also directly activate procaspase-7 in target cells.

Function and substrates: The active caspase-7 cleaves a broad set of cellular substrates, contributing to the orderly disassembly of the cell during apoptosis. Substrates include nuclear and cytoskeletal proteins and DNA-associated factors such as PARP, lamin A/C, and other structural components, leading to DNA fragmentation and morphological changes associated with cell death. Caspase-7 often acts in concert with caspase-3, with overlapping as well as distinct substrate specificities.

Genetics, expression, and regulation: In humans, the CASP7 gene encodes procaspase-7. It is widely expressed across tissues and resides mainly in the cytosol. Its activity is regulated by inhibitors of apoptosis (IAPs) such as XIAP and by various post-translational mechanisms.

Clinical relevance: Altered caspase-7 activity has been observed in certain cancers and neurodegenerative diseases. Research continues on modulating procaspase-7 activation or caspase-7 activity for therapeutic purposes in conditions where apoptosis is dysregulated.