The effector caspases drICE and dcp-1 have partially overlapping functions in the apoptotic pathway in Drosophila

Xu, Dongpo; Wang, Y; Willecke, Regina; Chen, Z; Tian, Di; Bergmann, Andreas

doi:10.1038/sj.cdd.4401920

Cited by 113 publications

(134 citation statements)

References 41 publications

(127 reference statements)

Supporting

Mentioning

124

Contrasting

Unclassified

Order By: Relevance

“…[12][13][14] In fact, mutants of diap1, dronc and drICE genes were isolated in genetic screens searching for modifiers of the eye ablation phenotypes caused by reaper or hid overexpression. [21][22][23][24][25][26][27] Mammalian IAP antagonists are Smac/Diablo and HtrA2/Omi, which function similarly to the RHG proteins. 28 Abbreviations: ALPS, autoimmune lymphoproliferative syndrome; APF, after puparium formation; Ced-3, cell death defective 3; CyO, curly of Oster; Dcp-1, death caspase 1; DIAP1, death-associated inhibitor of apoptosis 1; DNA, desoxyribonucleic acid; drICE, death-related ICE (interleukin converting enzyme); dronc, death regulator Nedd2-like caspase; EMS, ethyl methanesulfonate; Ey, eyeless; Flp, flippase; FRT82B, flippase recombination target at 82B; GFP, green fluorescent protein; Gh, GMR-hid; Hid, head involution defective; GMR, glass multimer reporter; HtrA2, high-temperature-required protein A2; IAP, inhibitor of apoptosis protein; PCR, polymerase chain reaction; R8, photoreceptor 8; RHG, reaper, hid, grim; Smac/Diablo, second mitochondria-derived activator of caspases/direct IAP binding protein with low pI; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling; Ubi, ubiquitous; wt, wild-type; XIAP, X-linked inhibitor of apoptosis…”

mentioning

confidence: 99%

mentioning

confidence: 99%

“…Although Dcp-1 has a crucial role in nurse cell death during mid-oogenesis, DrICE is required for apoptosis in most developmental and irradiation-induced cell death. 25,44,45 Four drICE mutants have been reported so far, only one of which, drICE 17 , is caused by a missense mutation. 25,44,46 drICE Δ1 , drICE Δ1E4 and drICE Δ2C8 were generated through imprecise P-element excisions, through which the entire drICE openreading frame was removed to produce null alleles.…”

mentioning

confidence: 99%

“…25,44,45 Four drICE mutants have been reported so far, only one of which, drICE 17 , is caused by a missense mutation. 25,44,46 drICE Δ1 , drICE Δ1E4 and drICE Δ2C8 were generated through imprecise P-element excisions, through which the entire drICE openreading frame was removed to produce null alleles. 44,46 drICE 17 carries an N to Y mutation at residue 116 and was isolated in an EMS mutagenesis screen as a recessive suppressor of the small eye phenotype induced by GMR-hid.…”

mentioning

confidence: 99%

“…This missense mutation leads to decreased protein stability and behaves as a strong hypomorphic allele. 25 These alleles have improved our understanding of the essential roles of drICE in developmental, stress-induced and RHG-induced cell death; 25,44,46 however, they have not provided information on how various amino-acid substitutions affect the behavior of the caspase protein.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Genetic characterization of two gain-of-function alleles of the effector caspase DrICE in Drosophila

Lindblad

Garnett

et al. 2015

Cell Death Differ

Self Cite

View full text Add to dashboard Cite

Caspases are the executioners of apoptosis. Although much is known about their physiological roles and structures, detailed analyses of missense mutations of caspases are lacking. As mutations within caspases are identified in various human diseases, the study of caspase mutants will help to elucidate how caspases interact with other components of the apoptosis pathway and how they may contribute to disease. DrICE is the major effector caspase in Drosophila required for developmental and stressinduced cell death. Here, we report the isolation and characterization of six de novo drICE mutants, all of which carry point mutations affecting amino acids conserved among caspases in various species. These six mutants behave as recessive loss-offunction mutants in a homozygous condition. Surprisingly, however, two of the newly isolated drICE alleles are gain-of-function mutants in a heterozygous condition, although they are loss-of-function mutants homozygously. Interestingly, they only behave as gain-of-function mutants in the presence of an apoptotic signal. These two alleles carry missense mutations affecting conserved amino acids in close proximity to the catalytic cysteine residue. This is the first time that viable gain-of-function alleles of caspases are described in any intact organism and provides a significant exception to the expectation that mutations of conserved amino acids always abolish the pro-apoptotic activity of caspases. We discuss models about how these mutations cause the gain-offunction character of these alleles. Cell Death and Differentiation (2016) 23, 723-732; doi:10.1038/cdd.2015.144; published online 6 November 2015Apoptosis is a major form of programmed cell death. 1 The core apoptotic machinery is evolutionary conserved with caspases as the fundamental components. [1][2][3] Caspases are specific cysteine proteases that are produced as inactive zymogens composed of an N-terminal pro-domain, a large subunit region with the catalytic cysteine residue, and a small subunit region at the carboxyl end. 2,4 Depending on their structures and functions, caspases are grouped into initiator and effector caspases. 2,3 Initiator caspases possess long pro-domains, which facilitate the recruitment of initiator caspases into cell death signaling complexes for activation. 2,3,5 Effector caspases are activated by initiator caspase complexes through proteolytic processing, cleaving off the pro-domain and separating the large and small subunits. The active effector caspase is a tetramer composed of two large and two small subunits and contains two catalytic sites. 2,3 Activated effector caspases cleave many protein targets to trigger the physiological and morphological changes characteristic of apoptosis. In mammals, apoptotic initiator caspases are Caspase-8, -9, -2 and -10, and effector caspases involved in apoptosis are 3 Of the seven Drosophila caspases, only the initiator caspase Dronc (Caspase-9-like) and the effector caspases DrICE and Dcp-1 (Caspase-3-like) have been implicated in apoptosis in imagina...

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Genetic characterization of two gain-of-function alleles of the effector caspase DrICE in Drosophila

Lindblad

Garnett

et al. 2015

Cell Death Differ

Self Cite

View full text Add to dashboard Cite

show abstract

Drosophila caspases involved in developmentally regulated programmed cell death of peptidergic neurons during early metamorphosis

Lee

Wang

Sehgal

et al. 2010

J of Comparative Neurology

View full text Add to dashboard Cite

A great number of obsolete larval neurons in the Drosophila central nervous system are eliminated by developmentally programmed cell death (PCD) during early metamorphosis. To elucidate the mechanisms of neuronal PCD occurring during this period, we undertook genetic dissection of seven currently known Drosophila caspases in the PCD of a group of interneurons (vCrz) that produce corazonin (Crz) neuropeptide in the ventral nerve cord. The molecular death program in the vCrz neurons initiates within 1 hour after pupariation, as demonstrated by the cytological signs of cell death and caspase activation. PCD was significantly suppressed in dronc-null mutants, but not in null mutants of either dredd or strica. A double mutation lacking both dronc and strica impaired PCD phenotype more severely than did a dronc mutation alone, but comparably to a triple dredd/strica/dronc mutation, indicating that dronc is a main initiator caspase, while strica plays a minor role that overlaps with dronc's. As for effector caspases, vCrz PCD requires both ice and dcp-1 functions, as they work cooperatively for a timely removal of the vCrz neurons. Interestingly, the activation of the Ice and Dcp-1 is not solely dependent on Dronc and Strica, implying an alternative pathway to activate the effectors. Two remaining effector caspase genes, decay and damm, found no apparent functions in the neuronal PCD, at least during early metamorphosis. Overall, our work revealed that vCrz PCD utilizes dronc, strica, dcp-1, and ice wherein the activation of Ice and Dcp-1 requires a novel pathway in addition to the initiator caspases.

show abstract

Mechanisms of Postecdysis‐Associated Programmed Cell Death of Peptidergic Neurons in Drosophila melanogaster

Lee

Kikuno

Nair

et al. 2013

J of Comparative Neurology

View full text Add to dashboard Cite

Crustacean cardioactive peptide (CCAP)-expressing neurons undergo programmed cell death (PCD) within 24 hours after adult eclosion. A subset of the doomed CCAP neurons in the ventral nerve cord also expressed the neuropeptide bursicon and thus are referred to as bursCCAP neurons. In this study, we undertook comprehensive genetic and transgenic analyses to dissect the PCD mechanisms of bursCCAP neurons. Expression of a versatile caspase inhibitor, p35, blocked PCD of bursCCAP neurons, suggesting caspase-dependent apoptosis. Further genetic analyses showed that Dronc/Dark and Drice are key caspases, but they are not sufficient to carry out the PCD fully. We did not find a role for other known caspases, Strica, Dredd, Damm, or Decay. Of interest, Dcp-1 is required not for the death of bursCCAP neurons per se but for the removal of neural projections. DIAP1 is an important survival factor that inhibits premature death of bursCCAP neurons. We found that grim functions as a principal death inducer, whereas other death genes, hid, reaper, and sickle, show no endogenous function. Taken together with other studies, our work supports the role of grim as a major death inducer particularly for the removal of obsolete larval neurons during CNS metamorphosis. Results from the ectopic expression of the mutant grim lacking either N-terminal IBM or internal GH3 domain indicated that both domains are necessary to induce CCAP cell death.

show abstract

The effector caspases drICE and dcp-1 have partially overlapping functions in the apoptotic pathway in Drosophila

Cited by 113 publications

References 41 publications

Genetic characterization of two gain-of-function alleles of the effector caspase DrICE in Drosophila

Genetic characterization of two gain-of-function alleles of the effector caspase DrICE in Drosophila

Drosophila caspases involved in developmentally regulated programmed cell death of peptidergic neurons during early metamorphosis

Mechanisms of Postecdysis‐Associated Programmed Cell Death of Peptidergic Neurons in Drosophila melanogaster

Contact Info

Product

Resources

About