CASP4

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CASP4

A gene on chromosome 11q22.2-q22.3 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. CASP4 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 highly expressed in the lung and spleen.
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There are subvariants of sensors and caspases, such as NLRP1, NLRP3, caspase-1, and caspase-4, marking variable inflammasomes with different biological functions.
Human caspase1, caspase-4, and caspase-5 are critical mediators in the pyroptosis process [7].
Here, we report an offense-defense mechanism that occurs during EHEC O:157 infection of the epithelium and show that NleF inhibits inflammatory cell death mediated by caspase-4. In this process, NleF prevents the production of IL-1[beta] and interrupts the heterodimerization of caspase-4-p19 and caspase-4-p10.
Recently, NleF has been reported to inhibit the catalytic activity of caspase-4, caspase-8, and caspase-9 [25].
EHEC [DELTA]nleF-Induced Inflammatory Cell Death Is Mediated by Caspase-4. To investigate which caspase is involved in [DELTA]nleF-induced inflammatory cell death, we used small interfering RNA (siRNA) to knock down caspase-1, caspase4, or caspase-5 in HT29 cells and then infected the cells with EDL933, [DELTA]nleF, or [DELTA]nleF/nleF.
The following antibodies were used according to the manufacturer's instructions: AIF (apoptosis-inducing factor), rabbit polyclonal; Bax, rabbit polyclonal; cytochrome c, mouse monoclonal; poly(ADP-ribose) polymerase (PARP), mouse monoclonal (BD PharMingen, San Diego, CA, USA); Bcl-2, mouse monoclonal (Santa Cruz Biotechnology, Santa Cruz, CA, USA); caspase-3, rabbit polyclonal (Assay Designs, Ann Arbor, MI, USA); caspase-4, caspase-8 and caspase-9, mouse monoclonal (Medical & Biological Laboratories, Nagoya, Japan); Smac/DIABLO, mouse monoclonal (BD Transduction Laboratories); [beta]-actin, mouse monoclonal (Sigma, Saint Louis, MO, USA).
Inflammatory caspases (caspase-1, caspase-4, caspase-5, and caspase-11) are critical for immune defenses [34-36].
In human cells, caspase-4 and caspase-5 performed the function of mouse caspase-11.
In contrast, noncanonical inflammasome activation requires species-specific inflammatory caspases other than caspase-1, particularly caspase-11 in mice [25] and caspase-4 and -5 in humans [26, 27].
[59] have observed noncanonical inflammasome activation via caspase-4 and caspase-11, respectively, in response to enteropathogens.
Caspase-1, in contrast to caspase-4, -5, and -11, is capable of processing interleukins [67].
The transcriptional control differs between the caspases of different species, e.g., it has been established for murine caspase-11 but not for human caspase-4, which is constitutively expressed [71].

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