CASP8

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CASP8

A gene on chromosome 2q33-q34 that encodes a protein belonging to the cysteine-aspartic acid protease (caspase) family which, once activated by proteolytic processing, plays a central role in the execution phase of cell apoptosis, as well as various stages of embryological development. CASP8 is an initiator-type caspase, which is activated by, and interacts with, upstream adaptor molecules through CARD and DED protein–protein interaction domains; it is involved in the programmed cell death induced by Fas and various apoptotic stimuli. It is highly expressed in peripheral blood leukocytes and in the spleen, thymus and liver.

Molecular pathology
CASP8 has been detected in the insoluble fraction of affected brain regions in Huntington disease, suggesting a role in neurodegenerative diseases.
References in periodicals archive ?
Apoptosis is classically signalled by two major apoptotic pathways (12) (Figure 2): the extrinsic pathway (also called the death receptor caspase-8 mediated pathway) and the intrinsic pathway (also called mitochondria-initiated caspase-9 pathway).
Caspase-8 triggers the production of inflammatory proteins that typically allow mammals to fight microbial infections.
Caspase activity was evaluated by measuring proteolytic cleavage of the chromogenic substrates DEVD-pNA (for caspase-3 like protease activity), IETD-pNA (for caspase-8 activity) and LEHD-pNA (for caspase-9 activity) as described previously (Rubio et al.
Further evidence confirming which of them is involved in the activation of caspase-3 is provided by the findings of elevated levels of caspase-8 and Fas, coupled with no alteration or even reduced levels of caspase-9 activity and cytosolic cytochrome c in ventricles of rats exposed to SHS (Figures 3 and 4).
Caspase-3 (Pharmingen, San Diego, CA), caspase-8 (FADD-like interleukin-1 beta-converting enzyme) and caspase-9-1ike Mch6 (MBL, Nagoya, Japan) activities were determined according to the manufacturer's protocol.
Upon binding, AT-406 induces rapid degradation of cIAP-1/2 proteins and promotes apoptosis through activation of caspase-8 and the death-receptor complex.
The investigators discovered this second role for caspase-8 while studying a genetic condition known to exist in only two people--a brother and sister found to have a mutation in both copies of their caspase8 genes.
The repeats, consisting of multiple copies of the amino acid glutamine, convert caspase-8 into an active form, according to test tube studies performed by the researchers.
Its effect on cellular morphology, cell cycle arrest, DNA fragmentation and expression levels of caspase-3, caspase-8 and caspase-9 were also determined.
Investigations of post-receptor signaling showed: caspase-8, Bid and Bax activation, increases in mitochondria permeability, cytochrome c release and caspase-9 activation.
Oligomerization of procaspase-8 in the DISC leads to self activation with release of active caspase-8 in to the cytosol.
Cleaved caspase-8 levels decreased significantly at all times, while cleaved caspase-3 was significantly decreased at 45 minutes.

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