Disease relevance of ced-3

• Restriction of vaccinia virus replication by a ced-3 and ced-4-dependent pathway in Caenorhabditis elegans [1].
• Programmed cell death mediated by ced-3 and ced-4 protects Caenorhabditis elegans from Salmonella typhimurium-mediated killing [2].
• Recently, we have demonstrated that interleukin 1beta-converting enzyme (ICE), a mammalian homologue of the Caenorhabditis elegans cell death gene ced-3, induces apoptotic cell death in malignant glioma cells [3].
• PURPOSE: To investigate whether interleukin-1beta-converting enzyme (ICE), a mammalian homologue of the Caenorhabditis elegans cell death gene ced-3, is involved in gamma-irradiation-induced apoptosis (programmed cell death) of human retinoblastoma cells [4].

High impact information on ced-3

• In a recent paper, reveal a new C. elegans death inhibitor, icd-1, whose loss can promote apoptosis independently of ced-3 [5].
• Most programmed cell deaths in the nematode C. elegans require ced-3 caspase activity [5].
• We have cloned the C. elegans cell death gene ced-3 [6].
• A ced-3 transcript is most abundant during embryogenesis, the stage during which most programmed cell deaths occur [6].
• The wild-type functions of the genes ced-3 and ced-4 are required for the initiation of programmed cell deaths in the nematode Caenorhabditis elegans [7].

Biological context of ced-3

• The genes ced-3 and ced-4 define the first known step of a developmental pathway for programmed cell death, suggesting that these genes may be involved in determining which cells die during C. elegans development [7].
• The ability of ced-3 and ced-4 alleles to restrict virus replication is correlated with their cell-killing activities [1].
• This Pn.p cell death is suppressed by mutations in the caspase gene ced-3 and in the bcl-2 homolog ced-9, suggesting that the Pn.p cells are dying by PCD in pvl-5 mutants [8].
• For example, lin-22 animals display transformations affecting entire postembryonic cell lineages, unc-86 animals are altered at an intermediate level of certain cell lineages, and ced-3 animals are affected only in the ultimate fates of cells produced by terminal cell divisions.(ABSTRACT TRUNCATED AT 400 WORDS)[9]
• Silencing of the rad-51 gene also causes a reduction in fecundity, which is suppressed by mutation in the DNA damage checkpoint gene rad-5, but not in the cell death effector gene ced-3 [10].

Anatomical context of ced-3

• In adult hermaphrodites, over 300 germ cells die, using the same apoptotic execution machinery (ced-3, ced-4 and ced-9) as the previously described 131 somatic cell deaths [11].
• Surprisingly, P. pacificus ced-3; lin-39 double mutants form a functional vulva in the absence of LIN-39 activity [12].
• Caspase-3, a vertebrate homologue of the protein encoded by the Caenorhabditis elegans cell death gene, ced-3, induces apoptosis when overexpressed in eukaryotic cells [13].

Associations of ced-3 with chemical compounds

• Vertebrate homologues of both ced-3 and ced-9 have been identified as the genes encoding the caspase cysteine proteases and the Bcl-2 family, respectively [14].

Regulatory relationships of ced-3

• The C. elegans gene product ced-9 inhibits programmed cell death by negatively regulating the death-mediating protease ced-3 [15].

Other interactions of ced-3

• To study the mechanism of lin-39 function, we isolated P. pacificus cell death mutants and identified mutations in ced-3 [12].

Analytical, diagnostic and therapeutic context of ced-3

• Since molecular cloning of the C. elegans ced-3 gene revealed its homology with mammalian IL-1beta-converting enzyme,1 14 members of the caspase family have been identified, which have often been involved as mediators of one or more phases of the apoptotic process [16].

References