country

Change Language

EN - English
FR - Français
DE - Deutsch
ES - Español
JA - 日本語
KO - 한국어

Product Name	Size / Unit Price	Qty

Total: USD 0.00 Checkout

Caspase-4

Definition:

Inflammatory caspase that acts as an essential effector of the NLRP3 and NLRP6 inflammasomes by mediating lipopolysaccharide (LPS)-induced pyroptosis. Thiol protease that cleaves a tetrapeptide after an Asp residue at position P1: catalyzes cleavage of CGAS, GSDMD and IL18. Required for innate immunity to cytosolic, but not vacuolar, bacteria (By similarity). Plays a key role in NLRP3-dependent CASP1 activation and IL1B and IL18 secretion in response to non-canonical activators, such as UVB radiation, cholera enterotoxin subunit B and cytosolic LPS. Activated by direct binding to LPS without the need of an upstream sensor. Involved in NLRP6 inflammasome-dependent activation in response to lipoteichoic acid (LTA), a cell-wall component of Gram-positive bacteria, which leads to CASP1 activation and IL1B and IL18 secretion. Independently of NLRP3 inflammasome and CASP1, promotes pyroptosis, through GSDMD cleavage and activation, followed by IL1A, IL18 and HMGB1 release in response to non-canonical inflammasome activators. Plays a crucial role in the restriction of Salmonella typhimurium replication in colonic epithelial cells during infection: in later stages of the infection, LPS from cytosolic Salmonella triggers CASP4 activation, which catalyzes cleavage of GSDMD, resulting in pyroptosis of infected cells and their extrusion into the gut lumen, as well as in IL18 secretion. Cleavage of GSDMD is not strictly dependent on the consensus cleavage site but depends on an exosite interface on CASP4 that recognizes and binds the Gasdermin-D, C-terminal (GSDMD-CT) part. Pyroptosis limits bacterial replication, while cytokine secretion promotes the recruitment and activation of immune cells and triggers mucosal inflammation. Involved in LPS-induced IL6 secretion; this activity may not require caspase enzymatic activity. Involved in cell death induced by endoplasmic reticulum stress and by treatment with cytotoxic APP peptides found in Alzheimer's patient brains. Catalyzes cleavage and maturation of IL18. In contrast, it does not directly process IL1B. During non-canonical inflammasome activation, cuts CGAS and may play a role in the regulation of antiviral innate immune activation.; (Microbial infection) In response to the Td92 surface protein of the periodontal pathogen T.denticola, activated by cathepsin CTSG which leads to production and secretion of IL1A and pyroptosis of gingival fibroblasts.

References:

[1]. Sonja Blasche, et al. The E. coli effector protein NleF is a caspase inhibitor. PLoS One. 2013;8(3):e58937. [Content Brief]

[2]. Yuji Kajiwara, et al. A critical role for human caspase-4 in endotoxin sensitivity. J Immunol. 2014 Jul 1;193(1):335-43. [Content Brief]

[3]. Gabriel Sollberger, et al. Caspase-4 is required for activation of inflammasomes. J Immunol. 2012 Feb 15;188(4):1992-2000. [Content Brief]

[4]. Zilin Li, et al. Shigella evades pyroptosis by arginine ADP-riboxanation of caspase-11. Nature. 2021 Nov;599(7884):290-295. [Content Brief]

[5]. Jianjin Shi, et al. Inflammatory caspases are innate immune receptors for intracellular LPS. Nature. 2014 Oct 9;514(7521):187-92. [Content Brief]

[6]. Jianjin Shi, et al. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature. 2015 Oct 29;526(7575):660-5. [Content Brief]

[7]. Kun Wang, et al. Structural Mechanism for GSDMD Targeting by Autoprocessed Caspases in Pyroptosis. Cell. 2020 Mar 5;180(5):941-955.e20. [Content Brief]

[8]. Elena Viganò, et al. Human caspase-4 and caspase-5 regulate the one-step non-canonical inflammasome activation in monocytes. Nat Commun. 2015 Oct 28;6:8761. [Content Brief]

[9]. Jonathan L Schmid-Burgk, et al. Caspase-4 mediates non-canonical activation of the NLRP3 inflammasome in human myeloid cells. Eur J Immunol. 2015 Oct;45(10):2911-7. [Content Brief]

[10]. Paul J Baker, et al. NLRP3 inflammasome activation downstream of cytoplasmic LPS recognition by both caspase-4 and caspase-5. Eur J Immunol. 2015 Oct;45(10):2918-26. [Content Brief]

[11]. C Faucheu, et al. A novel human protease similar to the interleukin-1 beta converting enzyme induces apoptosis in transfected cells. EMBO J. 1995 May 1;14(9):1914-22. [Content Brief]

[12]. Junichi Hitomi, et al. Involvement of caspase-4 in endoplasmic reticulum stress-induced apoptosis and Abeta-induced cell death. J Cell Biol. 2004 May 10;165(3):347-56. [Content Brief]

[13]. Yutao Wang, et al. Inflammasome Activation Triggers Caspase-1-Mediated Cleavage of cGAS to Regulate Responses to DNA Virus Infection. Immunity. 2017 Mar 21;46(3):393-404. [Content Brief]

[14]. Alessia Gaggero, et al. A novel isoform of pro-interleukin-18 expressed in ovarian tumors is resistant to caspase-1 and -4 processing. Oncogene. 2004 Sep 30;23(45):7552-60. [Content Brief]

[15]. Hye-Kyoung Jun, et al. Caspase-4 activation by a bacterial surface protein is mediated by cathepsin G in human gingival fibroblasts. Cell Death Differ. 2018 Feb;25(2):380-391. [Content Brief]

[16]. X X Tian, et al. NLRP6-caspase 4 inflammasome activation in response to cariogenic bacterial lipoteichoic acid in human dental pulp inflammation. Int Endod J. 2021 Jun;54(6):916-925. [Content Brief]

[17]. Chao Li, et al. Transmembrane Protein 214 (TMEM214) mediates endoplasmic reticulum stress-induced caspase 4 enzyme activation and apoptosis. J Biol Chem. 2013 Jun 14;288(24):17908-17. [Content Brief]

[18]. Cierra N Casson, et al. Human caspase-4 mediates noncanonical inflammasome activation against gram-negative bacterial pathogens. Proc Natl Acad Sci U S A. 2015 May 26;112(21):6688-93. [Content Brief]

[19]. N A Munday, et al. Molecular cloning and pro-apoptotic activity of ICErelII and ICErelIII, members of the ICE/CED-3 family of cysteine proteases. J Biol Chem. 1995 Jun 30;270(26):15870-6. [Content Brief]

[20]. J Kamens, et al. Identification and characterization of ICH-2, a novel member of the interleukin-1 beta-converting enzyme family of cysteine proteases. J Biol Chem. 1995 Jun 23;270(25):15250-6. [Content Brief]

[21]. Leigh A Knodler, et al. Noncanonical inflammasome activation of caspase-4/caspase-11 mediates epithelial defenses against enteric bacterial pathogens. Cell Host Microbe. 2014 Aug 13;16(2):249-256. [Content Brief]

Biomedical Dictionary

The Biomedical Dictionary is a comprehensive and professional collection of biological academic terms and subject datas. All explanations are supported by authoritative books or high impact factor literatures, and you can acquire accurate explanations of the biomedical terms you want to know.

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z #