Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.61 (caspase-8)
 6,833 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Programmed cell death, or apoptosis, is a process of fundamental importance to cellular homeostasis in metazoan organisms (Ellis, R. E., Yuan, J., and Horvitz, H. R. (1991) Annu. Rev. Cell Biol. 7, 663-698). The caspase family of mammalian proteases, related to the nematode death protein CED-3, plays a crucial role in apoptosis and inflammation. We report here the isolation and characterization of a new caspase, tentatively termed ERICE (Evolutionarily Related Interleukin-1beta Converting Enzyme). Based on phylogenetic analysis, ERICE (caspase-13) is a member of the ICE subfamily of caspases which includes caspase-1 (ICE), caspase-4 (ICErel-II, TX, ICH-2), and caspase-5 (ICErel-III, TY). Overexpression of ERICE induces apoptosis of 293 human embryonic kidney cells and MCF7 breast carcinoma cells. Like other members of the subfamily, ERICE is not activated by the serine protease granzyme B, a caspase-activating component of cytotoxic T cell granules. Therefore, ERICE most likely does not play a role in granzyme B-induced cell death. ERICE, however, was activated by caspase-8 (FLICE, MACH, Mch-5), the apical caspase activated upon engagement of death receptors belonging to the tumor necrosis factor family. This is consistent with a potential role for ERICE in this receptor-initiated death pathway.
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PMID:ERICE, a novel FLICE-activatable caspase. 962 66

The caspase (CASP) gene family is known to be involved in apoptosis, cytokine maturation, cell growth, and differentiation. A large number of single nucleotide polymorphisms (SNPs) in the CASP gene family have been increasingly recognized as important regulators in the development of lung cancer. However, this specific association is still controversial. In this Human Genome Epidemiology review and meta-analysis, we summarized the available evidence associating lung cancer with the CASP gene family. Seven studies, which included 1155 lung cancer cases and 1120 healthy controls, met the inclusion criteria and were included in our meta-analysis. In seven studies, 19 different SNPs have been studied in seven CASP genes, including CASP-1, -2, -5, -7, -8, -9, and -10. Meta-analysis results showed positive associations between heterozygote (A/G) of rs507879 in the CASP-5 gene, the T allele of rs12415607 in the CASP-7 gene, and the T allele and T carrier (C/T+T/T) of rs4645981 in the CASP-9 gene with lung cancer susceptibility [odds ratio (OR) = 1.83, 95% confidence interval (95%CI) = 1.07-3.12, P = 0.03; OR = 1.18, 95%CI = 1.02-1.37, P = 0.03; OR = 1.43, 95%CI = 1.12-1.81, P = 0.004; OR = 1.46, 95%CI = 1.10-1.93, P = 0.009; respectively]. However, we found that homozygote (G/G) of rs2227310 in the CASP-7 gene, del allele, heterozygote (ins/del), and del carrier (ins/del + del/del) of rs3834129 in CASP-8 could be protective factors for lung cancer (OR = 0.17, 95%CI = 0.14-0.21, P = 0.0003; OR = 0.83, 95%CI = 0.72-0.97, P = 0.02; OR = 0.74, 95%CI = 0.64-0.85, P < 0.0001; OR = 0.81, 95%CI = 0.71-0.93, P = 0.002; respectively). In conclusion, based on this meta-analysis, we suggest that SNPs in CASP-5, -7, -8, and -9 are associated with susceptibility to lung cancer.
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PMID:A literature-based systematic HuGE review and meta-analysis show that CASP gene family polymorphisms are associated with risk of lung cancer. 2331 81