Chinnaiyan AM et al. (1997) Nature "Role of CED-4 in the activation of CED-3."

Dixit VM, Chaudhary D, Chinnaiyan AM, Koonin EV, O'Rourke K

[Nature, 1997]

Genetic analyses of the nematode Caenorhabditis elegans have identified three core components of the cell-death apparatus. CED-3 and CED-4 promote, whereas CED-9 inhibits cell death. Recent studies indicate that CED-4 might interact independently with CED-3 and CED-9, forming the crux of a multicomponent death complex. But except for its role as an adaptor molecule, little is known about CED-4 function. A clue came with the observation that mutation of the phosphate-binding loop (P-loop) of CED-4 disrupts its ability to induce chromatin condensation in yeast. Further, a P-loop mutant of CED-4 (CED-4K165R) fails to process CED-3 in vivo, both in insect and mammalian cells (unpublished). We now confirm that CED-4 induces CED-3 activation and subsequent apoptosis, and that the process requires binding of ATP.

Silverman PH (1999) Science "C. elegans as a model."

Silverman PH

[Science, 1999]

Elizabeth Pennisi, in her excellent commentary "Worming secrets from the C. elegans" (News Focus, 11 Dec 1998, p.1972), states that "The first person to sense that the worm might take on such a prominent role in biology was molecular biologist Sydney Brenner." I am sure that Brenner would wish to acknowledge the role that Ellsworth C. Dougherty played in this matter. Dougherty originally described in 1949, "[a] new species of the free-living nematode genus Rhabditis of interest in comparative physiology and genetics".

Sung M et al. (2017) FEBS Lett "Depletion of cdc-25.3, a C. elegans ortholog of cdc25, increases physiological germline apoptosis."

Kawasaki I, Shim YH, Sung M

[FEBS Lett, 2017]

In Caenorhabditis elegans hermaphrodites, physiological germline apoptosis is higher in cdc-25.3 mutants than in wild type. The elevated germline apoptosis in cdc-25.3 mutants seems to be induced by accumulation of double-stranded DNA breaks (DSBs). Both DNA-damage and synapsis checkpoint genes are required to increase the germline apoptosis. Notably, the number of germ cells that lose P-granule components, PGL-1 and PGL-3, increase in cdc-25.3 mutants, and the increase in germline apoptosis requires the activity of SIR-2.1, a Sirtuin ortholog. These results suggest that elevation of germline apoptosis in cdc-25.3 mutants is induced by accumulation of DSBs, leading to a loss of PGL-1 and PGL-3 in germ cells, which promotes cytoplasmic translocation of SIR-2.1, and finally activates the core apoptotic machinery. This article is protected by copyright. All rights reserved.