[
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 Further, a P-loop mutant of CED-4 (CED-4K165R) fails to process CED-3 in vivo, both in insect and mammalian cells (unpublished).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.
[
Biophys Chem,
2005]
Lifespan regulation through gene expression involves complex biochemical processes. Unfortunately, current mathematical models for treating lifespan data afford little insight into the mechanisms that control longevity. In this work, we demonstrate the use of a novel kinetic model to successfully fit the lifespan curves of the nematode, Caenorhabditis elegans. Our findings show that population aging may be treated analogously to a dispersive chemical process [P.J. Skrdla, R.T. Robertson., J. Phys. Chem. B 109 10611 (2005)]. Much like the Gompertz model, only two fit parameters, alpha and beta, are needed to adequately describe the entire data set for each nematode population. These parameters relate a ''global first-order time constant'' and a ''global second-order rate constant'', with units of (time) and (time)(-2), respectively. In C. elegans, the increased longevity resulting from DAF-16 (a transcription factor) activity in the intestinal tissue correlates with a larger alpha value and a smaller beta value; the opposite is true for animals with shorter lifespans. A basic physical interpretation of the two parameters is provided.