Caspase3

Caspase-3, also known as caspase-3 (CASP3), is a cysteine-aspartic protease that serves as a key executioner in programmed cell death (apoptosis). It is synthesized as an inactive zymogen, procaspase-3, and is activated by proteolytic cleavage in response to pro-apoptotic signals. Initiator caspases such as caspase-8 (extrinsic pathway) and caspase-9 (intrinsic pathway) cleave procaspase-3 to generate an active enzyme composed of two subunits that assemble into a functional heterotetramer.

Caspase-3 cleaves a broad set of substrates implicated in apoptosis, including poly ADP-ribose polymerase (PARP), inhibitor of caspase-activated DNase (ICAD), and nuclear lamins, contributing to DNA fragmentation, cell shrinkage, and membrane blebbing. In addition to its canonical role in cell death, caspase-3 participates in non-apoptotic processes such as differentiation, neural development, and synaptic plasticity, with effects that depend on cellular context.

Regulation occurs at multiple levels, including inhibition by inhibitors of apoptosis (IAPs) such as XIAP, and activation downstream of mitochondrial cytochrome c release, apoptosome formation with Apaf-1, and caspase-9, or via death receptor signaling that converges on caspase-3. Aberrant caspase-3 activity has been linked to various diseases, including cancer, neurodegenerative disorders, and immune conditions.

The CASP3 gene encodes human caspase-3 and is located on chromosome 4q16.3. Enzymatic activity can be measured with peptide substrates such as DEVD-pNA or DEVD-based assays.