Disease relevance of CASP1

• The role of CASP1 genetic variations in the susceptibility to myocardial infarction requires further investigation [1].
• Inhibition of interleukin 1 beta-converting enzyme-mediated apoptosis of mammalian cells by baculovirus IAP [2].
• Interleukin-1 beta converting enzyme (ICE) or human immunodeficiency virus protease failed to induce DNA fragmentation in naive nuclei [3].
• Expression of interleukin 1 beta and interleukin 1 beta converting enzyme by intestinal macrophages in health and inflammatory bowel disease [4].
• We assessed the expression of several genes encoding pro-apoptotic cysteine proteases similar to interleukin-1 beta converting enzyme (ICE) and nematode Ced-3 in association with delayed neuronal death (DND) after transient forebrain ischemia in Mongolian gerbil [5].

Psychiatry related information on CASP1

• The increase in amplitude of P45 and N60 in MLSEPs seems to be characteristically associated with normal aging and the development of dementia [6].

High impact information on CASP1

• Overexpression of FADD in MCF7 and BJAB cells induces apoptosis, which, like Fas-induced apoptosis, is blocked by CrmA, a specific inhibitor of the interleukin-1 beta-converting enzyme [7].
• Crystal structure of the cysteine protease interleukin-1 beta-converting enzyme: a (p20/p10)2 homodimer [8].
• This proenzyme is related to interleukin-1 beta-converting enzyme (ICE) and CED-3, the product of a gene required for programmed cell death in Caenorhabditis elegans [9].
• Moreover, the interleukin-1 beta converting enzyme (ICE) family of cysteine proteases is now known to play a key role in apoptosis but has no discernible role in the cell cycle, arguing that the two processes are discrete [10].
• As suggested by earlier genetic analyses, a proteinase with properties resembling those of the interleukin-1-beta-converting enzyme (ICE) has been shown to initiate the apoptotic cascade in vitro [11].

Chemical compound and disease context of CASP1

• Interleukin-1 beta-converting enzyme mediates cisplatin-induced apoptosis in malignant glioma cells [12].
• We show here that cis-diamminedichloroplatinum (cisplatin) induces the expression of interleukin-1 beta-converting enzyme (ICE), a mammalian homologue of the Caenorhabiditis elegans cell death gene ced-3, in murine and human malignant glioma cells during apoptosis regardless of their p53 status [12].
• In this report we describe the purification to homogeneity of a 45-kDa protein (p45) that induces the differentiation of MDA-MB-453 human breast cancer cells and stimulates the tyrosine phosphorylation of p180erbB4, the HER4-encoded protein [13].
• To investigate a possible involvement of interleukin 1-beta-converting enzyme (ICE) or ICE-related proteases, we treated CEM-C7H2 sublines constitutively expressing the vaccinia virus protease inhibitor crmA with ceramide analogs [14].
• The HBeAg polypeptides (P15.5/16.5) derived from sera were physicochemically different from the two polypeptides with HBeAg activity (P19 and P45) liberated from Dane particle cores by the conventional method involving incubation with Nonidet P40 and 2-mercaptoethanol [15].

Biological context of CASP1

• In Europeans, 3 tag SNPs captured 4 common haplotypes of the CASP1 gene [1].
• A novel human protease similar to the interleukin-1 beta converting enzyme induces apoptosis in transfected cells [16].
• We have identified and characterized a novel cysteine protease named CMH-1 that is a new member of the interleukin 1 beta converting enzyme (ICE) family of proteases with substrate specificity for Asp-X [17].
• Upregulation of CASP genes is associated with an enhanced synthesis of related procaspases that precedes the appearance of apoptosis markers including caspase-3 activation, poly(ADP-ribose) polymerase cleavage and internucleosomal DNA fragmentation [18].
• Using the genomic IL1BC clone, we have confirmed the localization of the gene to chromosome 11 band q22.2-q22.3 by fluorescence in situ hybridization [19].

Anatomical context of CASP1

• Five alternatively spliced mRNA isoforms of human caspase-1 have been identified previously and we report here the cloning of a new isoform, named CASP1 zeta (zeta), from human ovarian surface epithelial cell cDNA [20].
• Nuclear run-on experiments demonstrate that etoposide increases CASP gene transcription in U937 cells, an effect that is prevented by Bcl-2 overexpression [18].
• DISC-associated active Fas-associated DD protein (FADD)-like interleukin-1 beta-converting enzyme-like protease (FLICE) also referred to as MACH/caspase 8 was only found in apoptosis-sensitive day 6 T cells [21].
• To understand the mechanism of interleukin-1 beta converting enzyme (ICE) activation in apoptosis, we analyzed the expression of ICE mRNA in two human cell lines by reverse transcription-polymerase chain reaction technique [22].
• BACKGROUND: In the lipopolysaccharide (LPS) stimulated peripheral blood monocyte, the precursor form of interleukin 1 beta (IL-1 beta, 31 kD) is processed by IL-1 beta converting enzyme (ICE) to the mature, bioactive form (17 kD) [4].

Associations of CASP1 with chemical compounds

• Cysteine proteases of the interleukin 1 beta Converting Enzyme (ICE)/CED-3 family have been implicated in the effector process of apoptosis in several systems, including Fas-mediated apoptosis [23].
• The active site Cys284 lies within a completely conserved stretch of 18 residues; however, Ser289 in hICE, which aligns with the catalytic region of serine and viral cysteinyl proteases, is absent from mICE [24].
• In contrast, Cytokine response modifier A (CrmA), a potent inhibitor of Interleukin-1 beta converting enzyme and related proteases, inhibited ceramide generation and prevented TNF-alpha-induced death [25].
• This effect was inhibited by the tetrapeptide Ac-DEVD-CHO, a competitive inhibitor of the interleukin-1 beta-converting enzyme (ICE)-related protease CPP32, but was not influenced by Ac-YVAD-CHO and Ac-YVAD-CMK, two specific inhibitors of ICE [26].
• This included the activation of interleukin 1 beta-converting enzyme (ICE)-like proteases with cleavage of the endogenous substrates poly(ADP ribose) polymerase and D4-GDI (GDP dissociation inhibitor for the rho family), as well as the fluorogenic peptide acetyl-Asp-Glu-Val-Asp-aminotrifluoromethylcoumarin (DEVD-AFC) [27].

Physical interactions of CASP1

• Purification of an interleukin-1 beta converting enzyme-related cysteine protease that cleaves sterol regulatory element-binding proteins between the leucine zipper and transmembrane domains [28].

Enzymatic interactions of CASP1

• Interleukin-1 beta converting enzyme (ICE) is a cysteine protease that catalyzes the conversion of the inactive precursor form of IL-1 beta to an active mature form [29].
• Although decreased snRNP-protein could be explained by decreased mRNA-steady state levels, another underlying mechanism might be suggested: snRNP is one of the death substrates rapidly cleaved during apoptosis by interleukin-1-beta-converting enzyme-like (ICE) proteases, which was well-documented by several groups [30].

Regulatory relationships of CASP1

• Lamins are, however, substrates for members of the interleukin-1 beta-converting enzyme (ICE) family of cysteine proteases that are activated during apoptosis and function downstream of Bcl-2 in the cell death pathway. lamins are degraded during E1A-induced p53-dependent apoptosis [31].
• BAX-induced cell death may not require interleukin 1 beta-converting enzyme-like proteases [27].
• The IL-1 beta-converting enzyme (caspase-1) inhibits apoptosis of inflammatory neutrophils through activation of IL-1 beta [32].
• Experiments with inhibitors for the proteases responsible for apoptosis signals showed that caspase 1 (IL-1 beta-converting enzyme) was not involved in apoptosis induced by IL-2 [33].
• Interleukin-1 beta converting enzyme-like protease involvement in Fas-induced and activation-induced peripheral blood T cell apoptosis in HIV infection. TNF-related apoptosis-inducing ligand can mediate activation-induced T cell death in HIV infection [34].

Other interactions of CASP1

• CPP32/apopain is a key interleukin 1 beta converting enzyme-like protease involved in Fas-mediated apoptosis [23].
• There was a clear improvement in alignment quality between CASP1 (1994) and CASP2 (1996) [35].
• Additionally, pro-apoptosis genes were down-regulated (e.g. twofold for CASP1, 2.5-fold for NALP7) with concomitant increased expression of the potential anti-apoptosis gene AKT3 [36].
• Whereas the precursor (pro) 31 kDa form of IL-1 alpha is biologically active, pro-IL-1 beta is inactive unless cleaved to its mature form by a cytoplasmic cysteine protease termed IL-1 beta converting enzyme (ICE) [37].
• Cleavage of poly(ADP-ribose) polymerase by interleukin-1 beta converting enzyme and its homologs TX and Nedd-2 [38].

Analytical, diagnostic and therapeutic context of CASP1

• Molecular cloning of the interleukin-1 beta converting enzyme [39].
• The interleukin-1 beta-converting enzyme (ICE) is localized on the external cell surface membranes and in the cytoplasmic ground substance of human monocytes by immuno-electron microscopy [40].
• Using immunoblots and enzyme-linked immunoassay for ICE, we demonstrate that alveolar macrophages do not differ from blood monocytes in antigenic p45 ICE [41].
• I kappa B, inhibitor of apoptosis protein (IAP)-1, and cellular Fas-associated death domain-like interleukin-1 beta-converting enzyme-like inhibitory protein (c-FLIP) expression was determined by Western blot [42].
• Association of bcl-2, bax, bcl-xL and interleukin-1 beta-converting enzyme expression with initial response to chemotherapy in acute myeloid leukemia [43].

References