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Gene Review:

ced-4 - Protein CED-4

Caenorhabditis elegans

Shaham, S. et al., Ellis, H.M. et al., Liu, W.H. et al., Yuan, J. et al., Subramaniam, K. et al., et al.

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Disease relevance of ced-4

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].

High impact information on ced-4

Our results suggest that the dual protective and killer functions of the C. elegans bcl-2-like gene ced-9 are mediated by inhibition of the killer and protective ced-4 functions, respectively [3].
The C. elegans gene ced-4 is essential for programmed cell death [3].
An alternatively spliced C. elegans ced-4 RNA encodes a novel cell death inhibitor [3].
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 [4].
In the absence of nos-1 and nos-2, germ cells cease proliferation at the end of the second larval stage, and die in a manner that is partially dependent on the apoptosis gene ced-4 [5].

Biological context of ced-4

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 [4].
The ability of ced-3 and ced-4 alleles to restrict virus replication is correlated with their cell-killing activities [1].
Surprisingly, the Pn.p cell death is not suppressed by loss of ced-4 function. ced-4 (Apaf-1) is required for all previously known apoptotic cell deaths in C. elegans [6].
When microinjected into a ced-4 animal, a 4.4 kb DNA fragment derived from the wild-type strain and corresponding to the region of the Tc4 insertion in the mutant ced-4(n1416) rescues the Ced-4 mutant phenotype [7].

Anatomical context of ced-4

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 [8].

Regulatory relationships of ced-4

We propose that a balance between opposing ced-4 functions influences the decision of a cell to live or to die by programmed cell death and that both ced-9 and ced-4 protective functions are required to prevent programmed cell death [3].

References

Restriction of vaccinia virus replication by a ced-3 and ced-4-dependent pathway in Caenorhabditis elegans. Liu, W.H., Lin, Y.L., Wang, J.P., Liou, W., Hou, R.F., Wu, Y.C., Liao, C.L. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
Programmed cell death mediated by ced-3 and ced-4 protects Caenorhabditis elegans from Salmonella typhimurium-mediated killing. Aballay, A., Ausubel, F.M. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
An alternatively spliced C. elegans ced-4 RNA encodes a novel cell death inhibitor. Shaham, S., Horvitz, H.R. Cell (1996) [Pubmed]
Genetic control of programmed cell death in the nematode C. elegans. Ellis, H.M., Horvitz, H.R. Cell (1986) [Pubmed]
nos-1 and nos-2, two genes related to Drosophila nanos, regulate primordial germ cell development and survival in Caenorhabditis elegans. Subramaniam, K., Seydoux, G. Development (1999) [Pubmed]
The Caenorhabditis elegans pvl-5 gene protects hypodermal cells from ced-3-dependent, ced-4-independent cell death. Joshi, P., Eisenmann, D.M. Genetics (2004) [Pubmed]
The Caenorhabditis elegans cell death gene ced-4 encodes a novel protein and is expressed during the period of extensive programmed cell death. Yuan, J., Horvitz, H.R. Development (1992) [Pubmed]
Genetic control of programmed cell death in the Caenorhabditis elegans hermaphrodite germline. Gumienny, T.L., Lambie, E., Hartwieg, E., Horvitz, H.R., Hengartner, M.O. Development (1999) [Pubmed]

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