First published online March 9, 2007
Development 134, 704e (2007)
© The Company of Biologists Limited
A time to die
Programmed cell death (PCD) is an important developmental process, but how
do cells know when it is time to die? Shai Shaham and co-workers now reveal
the role that the transcription factor PAL-1 and the caspase CED-3 play in C.
elegans tail-spike cell death
(p.1357). Cell death
in other C. elegans cells occurs via the EGL-1-mediated inhibition of CED-9, a
BCL-2 protein, which triggers the release of the caspase activator CED-4 to
cause CED-3 activation and cell death. The researchers show that PAL-1,
independently of CED-9 activity, binds to the ced-3 promoter to cause its
transcriptional induction. This induction immediately precedes cell death,
indicating that ced-3 transcription is the temporal cue for PCD initiation. In
pal-1 mutant worms, ced-3 is not upregulated and tail-spike PCD is prevented.
Because the mammalian homologue of PAL-1 is Cdx2, which, when mutated, can
cause intestinal tumours, the authors propose that by modulating Cdx2
expression, the overproliferation that is associated with intestinal cancers
could be targeted.
Related articles in Development:
- Timing of the onset of a developmental cell death is controlled by transcriptional induction of the C. elegans ced-3 caspase-encoding gene
- Carine W. Maurer, Michael Chiorazzi, and Shai Shaham
Development 2007 134: 1357-1368.
[Abstract]
[Full Text]
