Direct regulation of<i>egl-1</i>and of programmed cell death by the Hox protein MAB-5 and by CEH-20, a<i>C. elegans</i>homolog of Pbx1

Liu, Huarui; Strauss, Tamara J.; Potts, Malia B.; Cameron, Scott A.

doi:10.1242/dev.02234

Cited by 56 publications

(58 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent work showed that the Hox gene mab-5 is also required for the regulation of egl-1, and induction of apoptosis in the P11 and P12 cell lineages that generate neurons in the posterior ventral nerve cord. In the P11 lineage, MAB-5 forms a complex with the Pbx homologue CEH-20 to directly regulate egl-1 transcription [17].…”

Section: Transcription Is Importantmentioning

confidence: 99%

Pathways regulating apoptosis during patterning and development

Domingos

Steller

2007

Current Opinion in Genetics & Development

View full text Add to dashboard Cite

The patterning and development of multicellular organisms requires a precisely controlled balance between cell proliferation, differentiation and death. The regulation of apoptosis is an important aspect to achieve this balance, by eliminating unnecessary or mis-specified cells which, otherwise, may have harmful effects on the whole organism. Apoptosis is also important for the morphogenetic processes that occur during development and that lead to the sculpting of organs and other body structures. Here, we review recent progress in understanding how apoptosis is regulated during development, focusing on studies using Drosophila or C. elegans as model organisms.

show abstract

Section: Transcription Is Importantmentioning

confidence: 99%

Pathways regulating apoptosis during patterning and development

Domingos

Steller

2007

Current Opinion in Genetics & Development

View full text Add to dashboard Cite

show abstract

“…The cells P11.aaap (Pn.aaap, the posterior daughter of the anterior daughter of the anterior daughter of the anterior daughter of blast cell, Pn) and P12.aaap (referred to as 'P(11, 12).aaap'), are lineally equivalent to the more anteriorly located cells, P(1-10).aaap; however, P (11,12).aaap are programed to die, whereas P(1-10).aaap survive and differentiate into cholinergic motor neurons referred to as VB neurons. Scott Cameron et al (Liu et al, 2006) found that, in these lineages, the egl-1 expression also correlates with the observed pattern of cell death. Furthermore, they discovered that, in these lineages, Hox genes play an important role in Figure 4 Molecular model of the regulation of the NSM sister cell death.…”

Section: P11aaap and P12aaap: Turf Is Criticalmentioning

confidence: 96%

“…For example, mutations in the antennapedia-like mab-5 gene cause cell fate specification defects in the sub-lineages derived from blast cells, P11 and P12, but not from blast cells, P1-10 (Kenyon, 1986). Indeed, Cameron et al (Liu et al, 2006) found that mab-5 is specifically required for egl-1 expression in P11.aaap and P12.aaap (Liu et al, 2006). Furthermore, they obtained evidence that, at least in P11.aaap, the MAB-5 protein acts with the Hox co-activator, CEH-20, a member of the extradenticle/PBX TALE class of homeodomain proteins, to directly activate egl-1 transcription.…”

Section: S35mentioning

confidence: 99%

egl-1: a key activator of apoptotic cell death in C. elegans

Nehme

Conradt

2008

Oncogene

View full text Add to dashboard Cite

Since the discovery of mammalian BIK and BAD in 1995, BH3-only proteins have emerged as key activators of apoptotic cell death in animals as diverse as the nematode, Caenorhabditis elegans, and humans. BH3-only proteins have also emerged as integrators of cell-death signals that determine the life-versus-death decision and that transduce this decision to the central apoptotic machinery through their physical interaction with 'core' BCL-2 family members, such as BCL-2 or BCL-XL. Currently, eight BH3-only proteins have been identified and characterized in mammals, and there is evidence of functional overlap between them. In contrast, only two BH3-only proteins have so far been identified and characterized in C. elegans, EGL-1 and CED-13, and there seems to be only limited functional overlap between them. Combined with the powerful genetic tools available for the analysis of apoptosis in C. elegans, and the ability to study apoptosis at single-cell resolution in this organism, the absence of extensive functional redundancy makes C. elegans an ideal model for studies on BH3-only proteins. In this study, we will review our current understanding of the role and regulation of EGL-1. We will also briefly summarize studies on CED-13, which was identified more recently.Oncogene ( Keywords: BCL-2 family; BH3-only proteins; apoptosis; C. elegans; EGL-1; CED-13The egl-1 storyThe egl-1 gene was originally defined by dominant, gain of function (gf) mutations (Trent et al., 1983;Ellis and Horvitz, 1986). These gf mutations cause the hermaphrodite-specific neurons (referred to as 'HSNs'), which are required for egg laying in Caenorhabditis elegans hermaphrodites, to inappropriately die. egl-1 gf mutations were identified in screens for egg-laying defective or 'Egl' animals, and were carried out in Bob Horvitz's laboratory in the early 1980s (hence the name 'egl-1'). These 'Egl screens' resulted in the identification of a total of seven egl-1 gf mutations. Three of these mutations (n487, n1084 and n1796) cause an Egl phenotype in a semi-dominant manner, and the remaining four mutations (n986, n987, n2164 and n2248) cause an Egl phenotype in a fully dominant manner. The inappropriate death of the HSNs in egl-1 gf mutants can be suppressed by mutations that cause a general block in apoptotic cell death, such as a gf mutation in ced-9, which encodes an anti-apoptotic BCL-2-like protein, or loss-of-function (lf) mutations in either ced-4 or ced-3, which encode an APAF-1-like adapter or a caspase, respectively (Ellis and Horvitz, 1986;Hengartner et al., 1992;Yuan and Horvitz, 1992;Yuan et al., 1993;Hengartner and Horvitz, 1994b). These findings showed that the HSNs in egl-1 gf animals inappropriately die by apoptosis. They also suggested that the egl-1 gene may act upstream of the anti-apoptotic gene, ced-9, and of the pro-apoptotic genes, ced-4 and ced-3; however, the normal function of egl-1 remained unclear because of the lack of egl-1 lf mutations. The lack of egl-1 lf mutations not only made it difficult to determine the normal f...

show abstract

“…Indeed, studies of a small number of cells fated to die have shown that expression of egl-1 is under the control of known developmental transcription factors. [26][27][28][29][30][31] However, careful examination of the genetic interactions between C. elegans cell death genes suggests that the story is not so simple. If the linear model is correct, in double mutant animals containing both ced-9(lf) and ced-3(weak lf) alleles, the status of EGL-1 should be irrelevant, because its target, CED-9, is absent.…”

Section: The Canonical C Elegans Cell Death Programmentioning

confidence: 99%

Noncanonical cell death programs in the nematode Caenorhabditis elegans

2008

View full text Add to dashboard Cite

Genetic studies of the nematode Caenorhabditis elegans have uncovered four genes, egl-1 (BH3 only), ced-9 (Bcl-2 related), ced-4 (apoptosis protease activating factor-1), and ced-3 (caspase), which function in a linear pathway to promote developmental cell death in this organism. While this core pathway functions in many cells, recent studies suggest that additional regulators, acting on or in lieu of these core genes, can promote or inhibit the onset of cell death. Here, we discuss the evidence for these noncanonical mechanisms of C. elegans cell death control. We consider novel modes for regulating the core apoptosis genes, and describe a newly identified cell death pathway independent of all known C. elegans cell death genes. The existence of these noncanonical cell death programs suggests that organisms have evolved multiple ways to ensure appropriate cellular demise during development.

show abstract

Direct regulation ofegl-1and of programmed cell death by the Hox protein MAB-5 and by CEH-20, aC. eleganshomolog of Pbx1

Cited by 56 publications

References 51 publications

Pathways regulating apoptosis during patterning and development

Pathways regulating apoptosis during patterning and development

egl-1: a key activator of apoptotic cell death in C. elegans

Noncanonical cell death programs in the nematode Caenorhabditis elegans

Contact Info

Product

Resources

About