Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proteases of the caspase family, especially caspase-1 (ICE)(-like), caspase-3 (CPP32/Yama/apopain)(-like) and caspase-8 (MACH/FLICE/Mch5) proteases, are implicated in Fas (APO-1/CD95)-mediated apoptosis. Here, we show that the caspase-4 (TX/ICH-2/ICE(rel)II)(-like) protease, another member of the caspase family, is also involved in Fas-mediated apoptosis, based upon the observations: (i) caspase-4 is processed in response to an agonistic anti-Fas antibody treatment, (ii) overexpression of a mutant caspase-4 with active site mutations in both p20 and p10 subunits delays Fas-mediated apoptosis, (iii) microinjected anti-caspase-4 antibodies inhibit Fas-mediated apoptosis. Together with our observations that the mutant caspase-4 inhibits the Fas-mediated activation of caspase-3(-like) proteases and purified caspase-4 cleaves pro-caspase-3 to generate a subunit of active form, these results suggest that Fas-mediated apoptosis is driven by a caspase cascade in which the caspase-4(-like) protease transmits a death signal from caspase-8 to caspase-3(-like) proteases probably through directly cleaving pro-caspase-3(-like) proteases.
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PMID:Involvement of caspase-4(-like) protease in Fas-mediated apoptotic pathway. 923 63

Caspases are aspartate-specific cysteine proteases that play a pivotal role in drug-induced cell death. We designed RT-PCR assays to analyse the expression of CASP-3, CASP-4, CASP-6 and the long and short isoforms of CASP-2 genes in human cells. These genes heterogeneously coexpress in leukemic cell lines and bone marrow samples from patients with de novo acute myelogenous leukemia at diagnosis. Treatment of U937 and HL60 leukemic cells and HT29 colon carcinoma cells with the topoisomerase II inhibitor etoposide upregulates CASP-2 and CASP-3 genes in these cells before inducing their apoptosis. This effect of etoposide is not observed in K562 cells and bcl-2-transfected U937 cells which are less sensitive to drug-induced apoptosis. Nuclear run-on experiments demonstrate that etoposide increases CASP gene transcription in U937 cells, an effect that is prevented by Bcl-2 overexpression. 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. These results suggest that the ability of tumor cells to upregulate CASP-2 and CASP-3 genes in response to cytotoxic drugs could be predictive of their sensitivity to drug-induced apoptosis.
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PMID:Upregulation of CASP genes in human tumor cells undergoing etoposide-induced apoptosis. 967 9

Proteases of the caspase family are implicated in mammalian apoptosis and constitute a protease cascade. We characterized caspase-4 (TX/ICH-2/ICErelII) and caspase-5 (ICErelIII/TY), which are most closely related to caspase-1 (ICE) among the caspase family. Although overexpression of caspase-4 and caspase-5 induced apoptosis, confirming previous observations, this apoptosis was not inhibited by a caspase-1-specific tetrapeptide inhibitor (Ac-YVAD-CHO), suggesting that caspase-4 and caspase-5 have different substrate specificities from caspase-1 and also that caspase-4- and caspase-5-induced apoptosis is not mediated by caspase-1. CrmA, a cowpox virus-derived caspase-1 inhibitor that prevents apoptosis induced by various stimuli, was cleaved by caspase-4 and caspase-5, and inhibited their proteolytic activity as assessed by cleavage of pro-caspase-3 (pro-CPP32/Yama/apopain). Thus, caspase-4 and caspase-5 are CrmA-inhibitable proteases like caspase-1 and might be involved in apoptosis.
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PMID:Caspase-4 and caspase-5, members of the ICE/CED-3 family of cysteine proteases, are CrmA-inhibitable proteases. 1646 68