Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.36 (caspase-1)
 6,285 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antinuclear autoantibodies (ANAs) derived from patients with systemic autoimmune diseases have proven to be powerful tools in cell and molecular biology, The availability of these autoantibodies has been instrumental in the identification and characterization of a wide range of intracellular proteins involved in essential cellular activities. Recently, these autoantibodies have been used in molecular studies of apoptosis, particularly in the identification of substrates cleaved by proteases of the ICE/CED-3 family during this cell death pathway. The identification of these substrates may help to understand the role of proteolysis in apoptosis. Examples of nuclear autoantigens whose cleavage during apoptosis have been defined using ANAs include the 70 kD protein of the U1 small nuclear ribonucleoprotein particle (U1-70 kD), the nuclear mitotic apparatus protein (NuMA), DNA topoisomerase I, the RNA polymerase I upstream binding factor (UBF), and the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). The use of ANAs as probes for defining proteolytic events associated with apoptosis promises to yield important insights into the mechanisms driving this cell death pathway.
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PMID:Antinuclear autoantibodies: probes for defining proteolytic events associated with apoptosis. 911 31

NuMA is a component of the nuclear matrix which may play a structural role in the architecture of the interphase nucleus. During apoptosis NuMA is redistributed within the nucleus and is proteolysed from a 238-kDa form to a 180- to 200-kDa form. Here we show that the cleavage site leading to the stable fragment occurs between residues 1701 and 1725. Both the changes in morphology associated with apoptosis and the cleavage of NuMA were retarded by treatment with TPCK but not by treatment by other protease inhibitors including ICE inhibitor II.
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PMID:Cleavage of the nuclear matrix protein NuMA during apoptosis. 918 71

Apoptosis is initiated by activation of caspases (interleukin 1beta-converting enzyme homologues), which cause coordinated cleavage of several death substrates that function in structural or homeostatic pathways. The relationship between substrate cleavage and apoptosis is not yet known, nor is it clear whether cleavage of specific substrates is a critical requirement for apoptosis. The human neutrophil provides novel insights into the roles of proteolysis of specific substrates during apoptosis, since only a subset of caspase substrates are present in mature neutrophils. Of the death substrates we screened, PARP, the nuclear mitotic apparatus protein (NuMA), the 70 kDa subunit of the U1 small ribonucleoprotein (U1-70kDa) and the catalytic subunit of DNA-dependent protein kinase (DNA-PK(CS)) were not detected in non-apoptotic neutrophils; in contrast, lamin B and fodrin were present in amounts similar to those found in other cells. Caspase-3 activity was absent in freshly isolated neutrophils, but was detected when neutrophils were aged in vitro, coincident with the onset of morphologic and biochemical apoptosis. The absence of PARP, NuMA, U1-70kDa and DNA-PK(CS) in non-apoptotic neutrophils suggests that these are not critical anti-apoptotic proteins, and that their fragments are not required components of the neutrophil apoptotic pathway. These studies highlight the conserved role of caspase activation in the apoptotic mechanism, and focus attention on several conserved structural substrates as potential transducers of the proteolytic signal in apoptosis.
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PMID:Caspase-mediated proteolysis during apoptosis: insights from apoptotic neutrophils. 949 1

Orthopoxviruses encode three serpin homologs-SPI-1, SPI-2 and SPI-3-of which SPI-2 has been well characterized as an inhibitor of ICE-like proteases. A rabbitpox virus SPI-1 deletion mutant exhibited a host range restriction in human lung A549 and pig kidney 15 cell lines that was attributed to apoptosis. Here we report that replication of a vaccinia virus SPI-1 deletion mutant (DeltaSPI-1) was restricted in primary human keratinocytes as well as A549 cells. Although chromatin condensation was detected in some A549 cells, other morphological or biochemical signs of apoptosis including DNA fragmentation, cleavage of poly(ADP-ribose)polymerase or nuclear mitotic apparatus protein, or caspase 3 activation were not found. Moreover, DeltaSPI-1 protected A549 cells from apoptosis induced by tumor necrosis factor, whereas the corresponding DeltaSPI-2 mutant did not. Further studies indicated undiminished amounts of vaccinia virus early mRNA and replicated DNA in the absence of the SPI-1 product. However, there were reduced amounts of viral intermediate and late mRNAs, viral late proteins, cleaved core proteins, and virus particles. These data suggested that apoptosis is not the determining factor in the host range restriction of DeltaSPI-1 and that the SPI-1 gene product is needed to allow efficient expression of intermediate and late genes in A549 cells.
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PMID:Vaccinia virus serpin-1 deletion mutant exhibits a host range defect characterized by low levels of intermediate and late mRNAs. 1050 9