Programmed Cell Death and Its Regulation in C. e/egans
47
involved in regulating the death of all the 131 somatic cells that undergo
programmed cell death during C. elegans development.
The ces-2 gene has been cloned and encodes a basic region leucinezipper (bZIP) transcription factor most similar in its DNA-binding and
dimerization domain to the human hepatic leukemia factor, HLF
(Metzstein et al. 1996). An oncogenic form ofHLF found in a particular
form of pro-B-cell cancer (acute lymphoblastic leukemia), the E2AHLF fusion protein, is composed of the transactivation domain of E2A
and the DNA-binding domain of HLF and blocks the programmed cell
death of pro-B-cells (lnaba et al. 1996). It has been proposed that the
E2A-HLF fusion protein blocks programmed cell death by competing
with a CES-2-like factor for target sites in the promoter of a cell-death
promoting gene (Inaba et al. 1996; Metzstein et al. 1996). This finding
suggests that there might be conservation between C. elegans and mammals not only within the central cell-death pathway but also between the
components that regulate this pathway. No target gene of the CES-2
transcription factor has been characterized yet but it is likely that ces-J,
which acts downstream of ces-2 genetically, represents such a target.
One additional cell type-specific regulator of the central cell-death
pathway might have been discovered with the identification of gain-offunction mutations in egl-l. These gain-of-function mutations were
identified in screens for egg-laying defective mutants and initially defined the egl-l gene (Trent et al. 1983; Desai and Horvitz 1989). Gainof-function mutations in egl-l cause the inappropriate programmed cell
death of a pair of serotonergic motor neurons, the HSNs or hermaphrodite-specific neurons, which are required for egg laying in hermaphrodites (Sulston and Horvitz 1977). The phenotype of these gain-of-function mutations suggests that they affect the regulation of the egl-l gene
by a HSN-specific regulator of programmed cell death.
The identification of the ces-J gene, as well as the nature of the egl-l
gain-of-function mutations, has not been reported yet.
47
involved in regulating the death of all the 131 somatic cells that undergo
programmed cell death during C. elegans development.
The ces-2 gene has been cloned and encodes a basic region leucinezipper (bZIP) transcription factor most similar in its DNA-binding and
dimerization domain to the human hepatic leukemia factor, HLF
(Metzstein et al. 1996). An oncogenic form ofHLF found in a particular
form of pro-B-cell cancer (acute lymphoblastic leukemia), the E2AHLF fusion protein, is composed of the transactivation domain of E2A
and the DNA-binding domain of HLF and blocks the programmed cell
death of pro-B-cells (lnaba et al. 1996). It has been proposed that the
E2A-HLF fusion protein blocks programmed cell death by competing
with a CES-2-like factor for target sites in the promoter of a cell-death
promoting gene (Inaba et al. 1996; Metzstein et al. 1996). This finding
suggests that there might be conservation between C. elegans and mammals not only within the central cell-death pathway but also between the
components that regulate this pathway. No target gene of the CES-2
transcription factor has been characterized yet but it is likely that ces-J,
which acts downstream of ces-2 genetically, represents such a target.
One additional cell type-specific regulator of the central cell-death
pathway might have been discovered with the identification of gain-offunction mutations in egl-l. These gain-of-function mutations were
identified in screens for egg-laying defective mutants and initially defined the egl-l gene (Trent et al. 1983; Desai and Horvitz 1989). Gainof-function mutations in egl-l cause the inappropriate programmed cell
death of a pair of serotonergic motor neurons, the HSNs or hermaphrodite-specific neurons, which are required for egg laying in hermaphrodites (Sulston and Horvitz 1977). The phenotype of these gain-of-function mutations suggests that they affect the regulation of the egl-l gene
by a HSN-specific regulator of programmed cell death.
The identification of the ces-J gene, as well as the nature of the egl-l
gain-of-function mutations, has not been reported yet.