Caspase
Caspases were implicated in apoptosis with the discovery that CED-3, the product of a gene required for cell death in the nematode Caenorhabditis elegans, is related to mammalian interleukin-1b–converting enzyme (ICE or caspase-1). Caspases share similarities in amino acid sequence, structure, and substrate specificity. They are all expressed as proenzymes (30 to 50 kD) that contain three domains: an NH2-terminal domain, a large subunit (20 kD), and a small subunit (10 kD). Activation involves proteolytic processing between domains, followed by association of the large and small subunits to form a heterodimer.Caspases are among the most specific of proteases, with an unusual and absolute requirement for cleavage after aspartic acid. One role of caspases is to inactivate proteins that protect living cells from apoptosis. A clear example is the cleavage of ICAD/DFF45, an inhibitor of the nuclease responsible for DNA fragmentation, CAD (caspase-activated deoxyribonuclease).
ICAD is required for both the activity and inhibition of this nuclease, other negative regulators of apoptosis cleaved by caspases are Bcl-2 proteins. Caspases contribute to apoptosis through direct disassembly of cell structures, as illustrated by the destruction of nuclear lamina. Caspases also reorganize cell structures indirectly by cleaving several proteins involved in cytoskeleton regulation, including gelsolin, focal adhesion kinase (FAK), and p21-activated kinase 2 (PAK2). Death may be signaled by direct ligation of receptors at the cell surface, which leads to the activation of initiator caspases. These caspases then, directly or indirectly, activate the “executioner caspases”.Understanding how this signal can be recoupled to caspase activation may provide an opportunity to selectively kill transformed cells.
References
1.Thornberry NA,et al. Science. 1998 Aug 28;281(5381):1312-6. 2.Salvesen GS,et al. Cell. 1997 Nov 14;91(4):443-6.
ICAD is required for both the activity and inhibition of this nuclease, other negative regulators of apoptosis cleaved by caspases are Bcl-2 proteins. Caspases contribute to apoptosis through direct disassembly of cell structures, as illustrated by the destruction of nuclear lamina. Caspases also reorganize cell structures indirectly by cleaving several proteins involved in cytoskeleton regulation, including gelsolin, focal adhesion kinase (FAK), and p21-activated kinase 2 (PAK2). Death may be signaled by direct ligation of receptors at the cell surface, which leads to the activation of initiator caspases. These caspases then, directly or indirectly, activate the “executioner caspases”.Understanding how this signal can be recoupled to caspase activation may provide an opportunity to selectively kill transformed cells.
References
1.Thornberry NA,et al. Science. 1998 Aug 28;281(5381):1312-6. 2.Salvesen GS,et al. Cell. 1997 Nov 14;91(4):443-6.
Apoptosis
Caspase
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Lucidenic acid B
产品货号 : M37738
cas no: 95311-95-8
Lucidenic acid B 是从灵芝中分离得到的天然产物,可诱导肿瘤细胞凋亡,可产生 caspase-9 和 caspase-3 的活化和 PARP 的裂解。Lucidenic acid B 对细胞周期没有影响,且对坏死细胞无作用。 -
CIL62 B
产品货号 : M37542
cas no: 117593-36-9
CIL62 is a Necrostatin-1 dependent inducer of cell death through a caspase-3/7-independent mechanism. -
Ac-YVAD-AOM
产品货号 : M37204
cas no: 154674-81-4
Ac-YVAD-AOM 是 caspase-1 的抑制剂,具有抗肿瘤活性。 -
CZL55
产品货号 : M36542
cas no: 667408-87-9
CZL55 是 caspase-1 的抑制剂,IC50 为 24 nM。CZL55 可用于热性癫痫 (FS) 的研究。 -
MJN68390
产品货号 : M36320
cas no: 1956368-39-0
MJN68390 has an apparent IC50 value of 15 μM against CASP8 and shows no activity against CASP10.