Caspase 8

In the first installment of this two-part blog post titled "Apoptosis and Necroptosis: Important factors to identify both types of programmed cell death", the mechanisms by which cell death occurs and ways to identify these pathways were discussed. In this next segment, we focus on the molecular factors regulating the choice between programmed cell death and survival signaling.

Caspase-3 is one of the most important players in apoptosis signaling. It is synthesized as an inactive 32 kDa pro-enzyme and upon direct activation by Caspase-8, -9 or -10, it gets processed into its active forms, the p17-20 and p10-12 subunits. The latter are responsible for the cleavage of PARP (poly ADP-ribose polymerase), actin and SREBP, which are associated with apoptosis [1].

Survivin is an anti-apoptotic protein which is the smallest protein within a large family of proteins including X-linked IAP, c-IAP1 and 2, IAP-like protein-2, melanoma IAP, NAIP, and Livin. Survivin is responsible for a wide range of basic cellular functions that include the cell cycle regulation, fetal development, cell migration, and tumor progression.

Fas is a member of the tumor necrosis factor (TNF)-receptor superfamily and plays a key role in the physiological regulation of programmed cell death. This receptor contains a death domain which enables the formation of a signaling complex that includes Fas-associated death domain protein (FADD), caspase 8, and caspase 10. The auto-proteolytic processing of these complexed caspases triggers a downstream cascade that leads to membrane-mediated apoptosis.

Cell death via apoptosis is a fundamental cellular function triggered by the cell death receptor family and their ligands which signal through downstream adaptor molecules and the caspase protease family. All caspases exist in a precursor form composed of a prodomain, and large and small catalytic subunits. Caspases require a cleavage adjacent to an aspartate to liberate one large and one small subunit, which can then associate into an a2b2 tetramer.

Caspase 7 (also known as CASP7, Mch3, ICE-LAP3, CMH-1) is a member of caspase family of cysteine proteases. It is an apoptosis-related cystein peptidase encoded by the CASP7 gene in humans. CASP7 homologous sequences have been identified in nearly all mammals. Similar to Caspase 3, Caspase-7 is an effector caspase and plays a key role in apoptotic execution.

Apoptosis is one of the best-characterized phenomena in cellular and molecular biology. Not only is it essential for successful development, but its deregulation also leads to a number of human diseases, most notably cancer.

The caspases are a group of cysteine protease enzymes essential to apoptosis, inflammation and necrosis. Caspase 3 has been identified as one of the key mediators of apoptosis.

Caspase 3 is a member of the cysteine-aspartic acid protease family and an important mediator of apoptosis. Caspase 3 antibody reagents have been used in cancer, Alzheimer's disease and stem cell research. A recent caspase 3 antibody ELISA study showed elevated levels of the p17 caspase 3 fragment were associated with myocardial infarction in humans.