Caspase-1 Products

Description

Caspase-1, also known as interleukin-1-beta (IL-1beta) -converting enzyme (ICE), is a member of the cysteine-aspartic protease (caspase) family (1). The caspase family are aspartic proteolytic enzymes that play a key role in apoptotic cell death and inflammation (1). Caspase-1 is synthesized as an inactive proenzyme with a theoretical molecular weight of approximately 45 kDa and is 404 amino acids (aa) in length. The caspase-1 protein structure contains an N-terminal CARD (caspase recruitment domain), a large 20kDa P20 subunit (aa 120-297), and a small 10kDa P10 subunit (aa 317-404) (1, 2). The proenzyme undergoes cleavage at aspartic acid (Asp) residues to produce the active caspase-1 enzyme which exists as a heterotetramer (homodimer of the P20 and P10 heterodimers) (2). Inflammasome complexes sense various microbial and endogenous signals, including ligand-receptor interaction and growth factor deprivation, which results in the processing of pro-caspase to active caspase-1 (3, 4).The active caspase-1 is responsible for the cleavage and maturation of pro-inflammatory cytokines IL-1beta and IL-18, and promotes an inflammatory form of cell death induced by bacterial pathogens called pyroptosis (3, 4). Mature IL-1beta has a role in the immune reaction and recruiting inflammatory cells to the site of infection while IL-18 plays a role in interferon-gamma production and promotes cytolytic activity in natural killer cells (4).

Given the role of IL-1beta in inflammation, it makes sense that many diseases and pathologies have been associated with dysregulation of caspase-1 activation and the inflammasome (3, 4). The inflammasome is a multiprotein complex comprised of Nod-like receptor (NLR) family members and the adapter ASC (apoptosis-associated speck-like protein containing a CARD) which are crucial for capase-1 activation (3-5). For instance, the neuronal apoptosis inhibitory protein (NAIP)/NLRC4 inflammasome has been associated with colorectal cancer, breast cancer, and glioma pathogenesis (5). Caspase-1 activation and mutations in the inflammasome have also been linked to Chron's disease and Alzheimer's disease (4). In addition to immune and inflammatory related disorder, the inflammasome has been linked to metabolic and obesity related disorders including diabetes and cardiovascular disease (6). Finally, caspase-1 deficient mice exhibit enhanced epithelial cell proliferation in the colon, increased tumor formation, and reduced apoptosis (1). A more thorough understanding of the inflammasome-caspase-1 signaling pathway will be important for understanding disease pathology and potential therapeutic development.

Alternative names for caspase-1 includes CASP1, CASP1 nirs variant 1, EC 3.4.22.36, ICE, IL-1 beta-converting enzyme, IL1BC, IL1BCE, IL1B-converstase, interleukin-1 beta convertase, and p45.

References

1. Shalini, S., Dorstyn, L., Dawar, S., & Kumar, S. (2015). Old, new and emerging functions of caspases. Cell death and differentiation. https://doi.org/10.1038/cdd.2014.216

2. Chang, H. Y., & Yang, X. (2000). Proteases for cell suicide: functions and regulation of caspases. Microbiology and molecular biology reviews: MMBR. https://doi.org/10.1128/mmbr.64.4.821-846.2000

3. Vanaja, S. K., Rathinam, V. A., & Fitzgerald, K. A. (2015). Mechanisms of inflammasome activation: recent advances and novel insights. Trends in cell biology. https://doi.org/10.1016/j.tcb.2014.12.009

4. Franchi, L., Eigenbrod, T., Munoz-Planillo, R., & Nunez, G. (2009). The inflammasome: a caspase-1-activation platform that regulates immune responses and disease pathogenesis. Nature immunology. https://doi.org/10.1038/ni.1703

5. Kay, C., Wang, R., Kirkby, M., & Man, S. M. (2020). Molecular mechanisms activating the NAIP-NLRC4 inflammasome: Implications in infectious disease, autoinflammation, and cancer. Immunological reviews. https://doi.org/10.1111/imr.12906

6. Pham, D., Park, P. (2020). Recent insights on modulation of inflammasomes by adipokines: a critical event for the pathogenesis of obesity and metabolism-associated diseases. Archives of Pharmacal Research. https://doi.org/10.1007/s12272-020-01274-7

Bioinformatics

Entrez	12362 Mouse 25166 Rat 834 Human
Uniprot	AAH62327 Human NM_033292 Human NM_033293 Human NP_150634 Human NP_150634.1 Human NP_150635.1 Human NP_150636 Human P29466 Human
Alternate Names	CASP1 nirs variant 1 CASP1 CASP-1 caspase 1, apoptosis-related cysteine peptidase Caspase-1 subunit p10 Caspase-1 subunit p20 caspase-1 EC 3.4.22.36 EC:3.4.22.36 ICE IL-1 beta-converting enzyme IL1BC IL-1BC IL1BCE IL1B-convertase interleukin 1, beta, convertase interleukin 1-B converting enzyme Interleukin-1 beta convertase Interleukin-1 beta-converting enzyme p45

Research Areas for Caspase-1

Find related products by research area and learn more about each of the different research areas below.

Apoptosis
Cancer
Caspases