Caspase-9

[7] Caspase-9 belongs to a family of caspases, cysteine-aspartic proteases involved in apoptosis and cytokine signalling.

[6] Regulation of this enzyme occurs through phosphorylation by an allosteric inhibitor, inhibiting dimerization and inducing a conformational change.

[8] Correct caspase-9 function is required for apoptosis, leading to the normal development of the central nervous system.

Nonapoptotic roles of caspase-9 include regulation of necroptosis, cellular differentiation, innate immune response, sensory neuron maturation, mitochondrial homeostasis, corticospinal circuit organization, and ischemic vascular injury.

Increased caspase-9 activity is implicated in the progression of amyotrophic lateral sclerosis, retinal detachment, and slow-channel syndrome, as well as various other neurological, autoimmune, and cardiovascular disorders.

[12] The caspase-9 monomer consists of one large and one small subunit, both comprising the catalytic domain.

[13] Surface loops around the active site are short, giving rise to broad substrate specificity as the substrate-binding cleft is more open.

[8] Larger brains due to a decrease in apoptosis, resulting in an increase of extra neurons is an example of a phenotype seen in caspase-9 deficient mice.

[29] Certain polymorphisms in the promoter of caspase-9 enhances the rate at which caspase-9 is expressed, and this can increase a person's risk of lung cancer.

[19] In the context of graft versus host disease, caspase-9 can be introduced as an inducible switch.

Evidence shows that CAR T cells are effective in treating B-cell malignancies.

[32] One of the various ways to exert control over CAR T cell is through drug-controlled synthetic systems.

[33] If therapy with CAR T cells results in severe side effects, iCasp9 can be used to halt treatment.

[11][34] Caspase-9S doesn't have central catalytic domain, therefore it functions as an inhibitor of caspase-9α by attaching to the apoptosome, suppressing the caspase enzyme cascade and apoptosis.

Overview of signal transduction pathways involved in apoptosis .