What Is the Role of Caspase 3 in Apoptosis?

Caspase-3 is a protease. In 1994, Fernandez-Alnemri et al found a sequence homologous to the ICE / CED-3 active center in the expression sequence tag (EST) database of BenBank. After using it to synthesize a probe, A human Jurkat T lymphocyte cDNA library was screened, and a new gene was cloned from it. Because it encodes a cysteine protease with a molecular weight of 32 kD, it is called CPP32 (cysteine protease protein, 32 kD). Later, other scholars independently cloned this protein gene and named it prICE, apopain (apoptin), and Yama (the god of death in Indian legend). This protease was named caspase-3 in 1996. Caspase-3 is generally considered to be the main terminal cleaving enzyme in the process of apoptosis and an important part of the killing mechanism of CTL cells.

Caspase-3

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Caspase-3 is a protease. In 1994, Fernandez-Alnemri et al found a sequence homologous to the ICE / CED-3 active center in the expression sequence tag (EST) database of BenBank. After using it to synthesize a probe, A human Jurkat T lymphocyte cDNA library was screened, and a new gene was cloned from it. Because it encodes a cysteine protease with a molecular weight of 32 kD, it is called CPP32 (cysteine protease protein, 32 kD). Later, other scholars independently cloned this protein gene and named it prICE, apopain (apoptin), and Yama (the god of death in Indian legend). This protease was named caspase-3 in 1996. Caspase-3 is generally considered to be the main terminal cleaving enzyme in the process of apoptosis and an important part of the killing mechanism of CTL cells.

pro-caspase-3 contains 277 amino acid residues, with a molecular weight of about 32kD. It has 30% homology with ICE and 35% homology with CED-3.

Caspase-3 plays an irreplaceable role in apoptosis. Caspase-3 gene induces apoptosis after transfection of insect Sf9 cells. This process can be blocked by Bcl-2; it is removed in the extract of the cell that has undergone apoptosis After caspase-3, these extracts have lost their ability to induce apoptosis; adding purified caspase-3 again can restore the function of causing apoptosis. Caspase-3 can be activated by a variety of factors. In the killing effect of CTL cells, it can be activated by both the Fas / FasL pathway and the granzyme B pathway. Granzyme B is a serine esterase in CTL cell granules. It is the only protease that cleaves after Asp in mammals except caspase protease. It can specifically cleave the XXD sequence of the C-terminal protease of the ICE family of proteases And activate caspase 2, 3, 6, 7, 8, 9, 10. ICE can also be cleaved by granzymes, but is not activated after cleaving.

The main substrate of caspase-3 is poly (ADP-ribose) polymerase (PDP), which is related to DNA repair and gene integrity monitoring. At the initiation of apoptosis, 116kD PARP was cleaved by Asp216-Gly217 into 31kD and 85kD two fragments, so that the two zinc finger structures bound to DNA in PARP were separated from the carboxy-terminal catalytic region. Function properly. As a result, the activity of Ca ²⁺ / Mg ²⁺ dependent endonucleases affected by PARP negative regulation was increased, the DNA between nucleosomes was cleaved, and apoptosis was caused. This cleavage process can be inhibited by Ac-DEVD-CHO, a specific inhibitor of caspase-3, but not by CrmA.

caspase-3 can also cleave U1-70K, DNA-PK, PKCd and PKCq. Both PKCd and PKCq belong to the new PKC (novel PKC, nPKC). After being cleaved by caspase-3, the regulatory region can be excised to become the active form of PKC. In addition, experiments have shown that overexpression of PKCd and PKCq can cause cell decay. Death, indicating that they are all involved in the induction of apoptosis is an important part of the killing mechanism of CTL cells.