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When co-expressed, Reaper or Grim co-localized with cIAP1. Paper-1574299.
Deletion of this segment from either Reaper or Grim abolished binding to cIAPs. Paper-1574299.
Within this region are the genes for three pro-death proteins, Grim, Reaper and HID. Paper-9386385.
These results indicate that Reaper and Grim, but not HID, can activate DCP-1 in vivo. Paper-2175682.
Apoptosis triggered by rpr required intracellular Ca(2+) ions and calmodulin. Paper-8939064.
Apoptotic proteins Reaper and Grim induce stable inactivation in voltage-gated K+ channels. Paper-1587739.
A GH3 homology region is present in the Drosophila proapoptotic proteins Reaper and Sickle. Paper-9182236.
In addition to Reaper, Scythe binds two other Drosophila apoptotic regulators: Grim and Hid. Paper-8342406.
Silencing of Hid, Reaper, or Grim reduced caspase activation by apoptotic cell extract. Paper-12125949.
Dfd accomplishes this by directly activating the cell death promoting gene reaper ( rpr). Paper-9183412.
When ectopically expressed in the retina, Grim, Reaper and HID cause apoptosis and eye ablation. Paper-9386385.
It has been proposed that RPR, GRIM, and HID induce apoptosis by binding and inactivating TH/ DIAP1. Paper-2126039.
A genomic fragment upstream of rpr confers this regulatory behavior upon a lacZ reporter transgene. Paper-818282.
The RHG motifs of Drosophila Reaper and Grim are important for their distinct cell death-inducing abilities. Paper-8824988.
Following rpr overexpression, caspase activation-mediated apoptotic cell death was induced in the cells. Paper-8939064.
Molecular mechanisms of DrICE inhibition by DIAP1 and removal of inhibition by Reaper, Hid and Grim. Paper-10241836.
The dynamin-related protein, Drp1, is important for Reaper- and DNA-damage-induced mitochondrial disruption. Paper-13226482.
These results suggest that Reaper and Grim may participate in initiating apoptosis by stably blocking K+ channels. Paper-1587739.
The pro-death proteins Reaper, Hid and Grim (RHG) induce apoptosis by antagonizing DIAP1 function. Paper-10241836.
The pro-death proteins Reaper, Hid and Grim (RHG) promote apoptosis by antagonizing DIAP1 function. Paper-10040775.
The GH3 domain and the homologous regions in Reaper and Sickle are predicted to be structured as amphipathic alpha-helixes. Paper-9182236.
The physical interaction of IAPs with RPR provides a molecular mechanism for IAP inhibition of RPR's apoptotic activity. Paper-1176059.
Importantly, we show that mitochondrial targeting of DIAP1 alone is not sufficient for degradation and requires Reaper binding. Paper-12673938.
Cells in which cytochrome c expression was decreased underwent apoptosis induced by stress stimuli, Reaper or Grim. Paper-9182137.
The reaper ( rpr) and head involution defective (hid) genes mediate programmed cell death (PCD) during Drosophila development. Paper-9181499.
Previous genetic studies have established Reaper and Grim as central regulators of apoptosis in Drosophila melanogaster. Paper-1574299.
In addition, Reaper and Grim, but not Hid induced apoptosis is sensitive to a reduction of DRONC levels. Paper-11489467.
This may reflect a requirement to block maternally provided RPR and HID, or it may indicate another function of the TH/ DIAP1 protein. Paper-2126039.
The proapoptotic genes reaper ( rpr), grim, and head involution defective (hid) are required for virtually all embryonic apoptosis. Paper-2126039.
Thus, apoptosis initiated by Reaper progressed by a faster path which appeared to differ from that of FADD-induced apoptosis. Paper-859903.
Drosophila Reaper can bind inhibitor of apoptosis proteins ( IAP) and thereby rescue caspases from proteasomal degradation. Paper-10496345.
Artificial compensatory proliferation induced by coexpression of Reaper and p35 was completely suppressed in dronc mutants. Paper-12232616.
In this study, we show for the first time that ectopic expression of Reaper or Grim induced substantial apoptosis in mammalian cells. Paper-1574299.
This ubiquitination of Reaper requires IAP ubiquitin-ligase activity and a stable interaction between Reaper and the IAP. Paper-9657829.
Here we show that HID blocks DIAP1's ability to inhibit caspase activity and provide evidence suggesting that RPR and GRIM can act similarly. Paper-1983997.
The central cell death regulators Reaper and Hid induce apoptosis very rapidly by inhibiting DIAP1 function. Paper-10564168.
Developmentally regulated apoptosis in Drosophila requires the activity of the reaper ( rpr), grim and head involution defective (hid) genes. Paper-9181605.
Three proteins, Hid, Grim, and Reaper, promote apoptosis, in part by binding to DIAP1 through their conserved N-terminal sequences. Paper-9031107.
We have analyzed the importance of the RHG motifs in Reaper and Grim for their different abilities to activate cell death during development. Paper-8824988.
Structure/function analysis of Reaper has identified an extreme N-terminal motif that appears to be sufficient for inhibition of IAP function. Paper-10040778.
Moreover, ectopic cell killing by the Drosophila cell-death activators, Reaper, Grim and Hid, is substantially suppressed in dark mutants. Paper-8341745.
Drosophila activators of apoptosis mapping to the Reaper region function, in part, by antagonizing IAP proteins through a shared RHG motif. Paper-10459483.
Loss of mir-14 enhances Reaper-dependent cell death, whereas ectopic expression suppresses cell death induced by multiple stimuli. Paper-10022461.
Through direct binding, Reaper can bring the Drosophila IAP ( DIAP1) to mitochondria, concomitantly promoting IAP auto-ubiquitination and destruction. Paper-12673938.
Here we show that rpr is induced directly by the ecdysone-receptor complex through an essential response element in the rpr promoter. Paper-8468318.
Cell killing by grim was blocked by coexpression of p35, a viral product that inactivates ICE-like proteases, and did not require the functions of rpr or hid. Paper-609266.
However, genetic mosaic analysis of adult photoreceptors lacking rpr, hid, and grim show that these PCD inducers are not required for norpA degeneration. Paper-10392985.
In Drosophila melanogaster, the induction of apoptosis requires three closely linked genes, reaper ( rpr), head involution defective (hid), and grim. Paper-2175682.
The physical interaction of IAPs with RPR, HID, and GRIM provides a common molecular mechanism for IAP inhibition of these Drosophila proapoptotic proteins. Paper-1444714.
Induction of apoptosis by rpr overexpression or by cycloheximide or etoposide treatment of Drosophila cells results in proteolytic processing of drICE. Paper-1046788.
The anti-apoptotic baculoviral P35 protein acts downstream of hid activity to suppress the photoreceptor cell death driven by rpr and hid. Paper-9181499.
Different signals trigger the novel death regulators rpr, hid, and grim, that utilize the evolutionarily conserved iap and ark genes to modulate caspase function. Paper-8547043.
We demonstrate that the N-end rule pathway is required for regulation of apoptosis induced by Reaper and Hid expression in the Drosophila melanogaster eye. Paper-9698125.
Independent of caspase activation, Bunyavirus NSs proteins also share with Reaper the ability to directly inhibit cellular protein translation. Paper-10009253.
The L22 nt sequence is about 70% similar to the mammalian L27a rp mRNA and about 60% homologous to the Drosophila, Tetrahymena and yeast corresponding mRNAs. Paper-182080.
Here, we show that Drosophila mitochondria become permeable in response to the expression of Reaper and Hid, endogenous regulators of developmental apoptosis. Paper-13226482.
Additionally, in vivo binding studies demonstrated that both Reaper and Grim physically interacted with human IAPs through a homologous 15-amino acid N-terminal segment. Paper-1574299.
Novel mechanisms were proclaimed in recent months for some important regulatory proteins from Drosophila (e.g. Bruno, Sex-lethal, Reaper), but the evidence is thin. Paper-12275906.
Expression of P35, a caspase inhibitor, also blocked RPR-induced apoptosis and delayed RPR decline, but RPR remained cytoplasmic in its location. Paper-1176059.
Therefore X. laevis L22 mRNA is a new example of the correlation between the polypyrimidine terminal tract and the translational regulation observed in other rp mRNAs. Paper-182080.
The levels of ecdysone-inducible transcripts such as E75A and Reaper (Rpr) are normal in the absence of DRONC, suggesting that DRONC acts downstream of these genes. Paper-11489467.
Instead, a second IAP-binding domain, distinct from the R3, was identified at the C terminus of Reaper that bound to DIAP1 but failed to trigger apoptosis. Paper-10459483.
The 510-bp L22 cDNA sequence presents short untranslated regions and a 5'-end polypyrimidine tract found in all other vertebrate r-protein mRNA ( rp mRNA) so far analyzed. Paper-182080.
The 5' end of the D. melanogaster rpL17A mRNA contains a polypyrimidine tract displayed by several mammalian rp genes and involved in translational control of their expression. Paper-68821.
We show that expression of either rpr or hid under control of a rhodopsin promoter induces rapid cell death of adult photoreceptor cells. Paper-9181499.
Interestingly, bcl-2 suppresses both bax- and rpr- induced mitochondrial defects while the caspase-inhibitor p35 is specific to the rpr pathway. Paper-9186057.
Finally we analyzed the function of a truncated Reaper- C protein which lacks the NH2-terminal 14 amino acids that are conserved between Reaper, Hid, and Grim. Paper-1665549.
A stereotypic series of cellular changes occur during apoptosis, most of which are initiated by a caspase cascade that is triggered by a trio of proteins, RPR, HID and GRIM. Paper-10066223.
Finally, diap2 is repressed by ecdysone in cultured salivary glands under the same conditions that induce rpr expression and trigger programmed cell death. Paper-1274493.
Moreover, by virtue of this interaction, we demonstrate that cIAPs can regulate Reaper and Grim by abrogating their ability to activate caspases and thereby inhibit apoptosis. Paper-1574299.
The positive regulators, reaper ( rpr), head involution defective (hid) and grim, as well as the negative regulators, DIAP1 and DIAP2, are transcribed during oogenesis. Paper-1389971.
The E93 gene is necessary for ectopic salivary gland cell destruction, and ectopic rpr, dronc, and crq transcription, that is induced by expression of betaFTZ-F1. Paper-9271522.
Dying midguts express the rpr, hid, ark, dronc, and crq cell death genes, suggesting that the core cell death machinery is involved in larval midgut cell death. Paper-9368990.
Expression of IAPs blocked RPR- induced apoptosis and resulted in the accumulation of RPR in punctate perinuclear locations which coincided with IAP localization. Paper-1176059.
Nevertheless, we find that Reaper efficiently induces apoptosis in mammalian cells in the absence of mitochondrial permeabilisation and cytochrome c release. Paper-10496345.
We identified a new activator of apoptosis, grim, which maps between two previously identified cell death genes in this region reaper ( rpr) and head involution defective (hid). Paper-609266.
In vitro binding experiments indicated that Reaper and Grim bound specifically to the BIR domain-containing region of cIAPs as deletion of this region resulted in loss of binding. Paper-1574299.
Inhibitors of ICE-family proteases p35 and crmA, as well as members of the iap class of genes, Op-iap and D-iap2, but not bcl-2 family members, blocked rpr-induced apoptosis. Paper-859903.
Our results indicate that once induced, dp53 amplifies and sustains the response through a positive feedback loop with Dronc and the apoptosis- inducing factors Hid and Reaper. Paper-12184263.
The proapoptotic factors Reaper, Hid, Grim, and Sickle regulate apoptosis in Drosophila by inhibiting the antiapoptotic factor DIAP1 (Drosophila inhibitor of apoptosis 1). Paper-12948647.
Drosophila Reaper ( RPR), Head Involution Defective (HID), and GRIM induce caspase-dependent cell death and physically interact with the cell death inhibitor DIAP1. Paper-1983997.
Overexpression of DIAP1 or a related protein, DIAP2, in the eye suppresses normally occurring cell death as well as death due to overexpression of rpr or head involution defective. Paper-466551.
Conversely, Reaper able to bind IAPs, but lacking a mitochondrial targeting GH3 domain (DeltaGH3 Reaper), can induce DIAP1 turnover only if DIAP1 is otherwise targeted to membranes. Paper-12673938.
The death inducers Reaper, Grim and Hid relay signals, possibly through IAPs (inhibitor of apoptosis proteins) and Dark (an Apaf-1/Ced-4 homologue), to trigger caspase function. Paper-8328167.
Coordinate stage-specific induction of the Drosophila death genes reaper ( rpr) and head involution defective (hid) immediately precedes the destruction of the larval midgut and salivary gland. Paper-1274493.
DIABLO is a mammalian protein that can bind to IAPs and antagonize their antiapoptotic effect, a function analogous to that of the proapoptotic Drosophila molecules, Grim, Reaper, and HID. Paper-8758458.
Caspase activation in the absence of Reaper and Hid is not sufficient to permeabilize mitochondria, but caspases play a role in Reaper- and Hid-induced mitochondrial changes. Paper-13226482.
Deletion of 20 amino acids from the carboxy-terminus of Reaper fully abrogated its potential to inhibit protein synthesis and to induce apoptosis in the absence of IAP-binding. Paper-10496345.
Analysis of chimeric R/ Grim and G/ Reaper proteins indicated that the Reaper and Grim RHG motifs are functionally distinct and help to determine specific cell death activation properties. Paper-8824988.
Here we show through a genetic screen that a mutant of Drosophila melanogaster tumour-necrosis factor receptor-associated factor 1 ( DTRAF1) is a dominant suppressor of Reaper-induced cell death. Paper-9183426.
Decreased activity of this pathway enhances, and increased activity suppresses, apoptosis induced by ectopic expression of the cell death regulators reaper ( rpr) and head involution defective (hid). Paper-1638352.
In addition, the diap2 anti-cell death gene is repressed in larval salivary glands as rpr and hid are induced, suggesting that the death of this tissue is under both positive and negative regulation. Paper-1274493.
Drosophila Reaper, a regulator of developmental cell death, acts on IAP (inhibitor of apoptosis) proteins to activate caspases, but can regulate mitochondrial permeability in vitro. Paper-10200512.
By the features described, the clones we have isolated identify the Drosophila rp gene homologous to the L1 rp gene of Xenopus and could code for the L1 ribosomal protein described in D. melanogaster. Paper-5828674.
In Drosophila, the chromosomal region 75C1-2 contains at least three genes, reaper ( rpr), head involution defective (hid), and grim, that have important functions in the activation of programmed cell death. Paper-1010999.
We generated DIAP1-depleted embryos by either using homozygous null mutants for thread, the gene coding DIAP1, or by ectopically expressing in early embryos the RGH protein Reaper, which inhibits DIAP1. Paper-13349092.
Analyses of BR-C, E74A, and E93 loss-of- function mutants indicate that these genes regulate stage-specific transcription of the rpr, hid, ark, dronc, and crq cell death genes. Paper-9271522.
Although both the ecdysone hormone receptor complex and p53 directly regulate rpr transcription, rpr was found to play a limited role in inducing apoptosis in response to either of these signals. Paper-9181605.
However, in response to apoptotic signals, Reaper-family proteins are produced, which promote the auto-ubiquitination and degradation of Diap1, thereby removing the 'brakes on death' in cells that are doomed to die. Paper-12833463.
We showed previously that ectopic expression of either rpr or hid triggers rapid PCD in adult photoreceptors, and this is completely suppressed by the coexpression of the baculoviral P35 caspase inhibitor. Paper-10392985.
GMR-Gal4-driven RNAi for Hsp60D in developing eyes dominantly suppressed cell death caused by expression of Reaper, Hid, or Grim (RHG), the key activators of canonical cell death pathway. Paper-13045648.
Significantly, we show that inhibition of Reaper or Hid mitochondrial localization or inhibition of Drp1 significantly inhibits apoptosis, indicating a role for mitochondrial disruption in fly apoptosis. Paper-13226482.
Apoptosis initiates when proteins such as Reaper, Hid, and Grim bind a surface groove in DIAP1 baculovirus IAP repeat domains via an N-terminal IAP-binding motif. Paper-12424773.
Recently a Drosophila p53 protein has been identified that mediates apoptosis via a novel pathway involving the activation of the Reaper gene and subsequent inhibition of the inhibitors of apoptosis (IAPs). Paper-9707086.
Moreover, we have identified a small region of Reaper, similar to the GH3 domain of Grim, that is required for localization of Reaper to mitochondria, induction of IAP degradation, and potent cell killing. Paper-10040778.
This response is preceded by an ecdysone-triggered switch in gene expression in which the diap2 death inhibitor is repressed and the reaper ( rpr) and head involution defective (hid) death activators are induced. Paper-8468318.
Here, we present an analysis of loss-of-function and gain-of-function alleles of th, which indicates that additional domains of TH/ DIAP1 are necessary for its ability to inhibit death induced by RPR, GRIM, and HID. Paper-2126039.
A mutation in the homeobox gene sine oculis (so) that ablates the larval visual system, or the targeted expression of the reaper ( rpr) cell death gene, abolishes all responses to light detected as a change of direction. Paper-1820458.
This loss-of-ventral-eye phenotype can be rescued by (i) increasing the levels of cell death inhibitors, (ii) reducing the levels of Hid- Reaper- Grim complex, or (iii) reducing canonical Wg signaling components. Paper-12306654.
The mammalian cDNA encoding FADD (Fas-associating protein with a death domain) also induced cell death in SF-21 cells, but death progressed more slowly and with features which distinguished it from rpr-induced apoptosis. Paper-859903.
In Drosophila, patterns of programmed cell death have been studied, and it is known that the induction of apoptosis requires the products of three closely linked genes, reaper ( rpr), head involution defective (hid) and grim. Paper-10019608.
We recently reported that Reaper- induced mitochondrial cytochrome c release and caspase activation in a cell-free extract of Xenopus eggs requires the presence of a 150 kDa Reaper-binding protein, Scythe. Paper-8342406.
Based on these results, we propose that RPR, HID, and GRIM promote apoptosis by disrupting productive IAP- caspase interactions and that DIAP1 is required to block apoptosis- inducing caspase activity. Paper-1983997.
Like apoptosis in earlier developmental stages, this unique communal form of cell death is controlled through the apoptosome proteins, Dronc and Dark, together with the IAP antagonists, Reaper, Grim, and Hid. Paper-13387358.
The transcription of rpr, hid, and crq are altered in BR-C mutants, and E93 mutants possess altered transcription of the caspase dronc, providing a mechanism for the disruption of midgut cell death in these mutant animals. Paper-9368990.
In addition, the phenotypes caused by the overexpression of DmRad51 were similar to those caused by ectopic expression of Reaper, a proapoptotic protein, and were partially suppressed by the coexpression of p35, an antiapoptotic protein. Paper-10495127.
Mutations in the N-terminal region of Reaper, which displays sequence similarity to Hid and Grim, other Drosophila gene products correlated with the initiation of apoptosis, suggested that these residues might be functionally important. Paper-859903.
Conversely, targeted expression of GlcT-1 partially rescued cell death caused by the proapoptotic factors Reaper and Grim, suggesting that ceramide generation might be one signal pathway that executes the cell death program. Paper-10534102.
We show that mutations in thread ( th) are dominant enhancers of RPR- induced cell death and that th encodes a protein homologous to baculovirus inhibitors of apoptosis (IAPs), which we call Drosophila IAP1 ( DIAP1). Paper-466551.
Because cell death induced by the protein encoded by rpr ( RPR) could be blocked by the baculovirus p35 protein, RPR appears to activate a death program mediated by a ced-3/ICE (interleukin-1 converting enzyme)-like protease. Paper-541998.
As in the Drosophila proteins Reaper, Grim and Hid, the amino-terminal amino acids of Smac/ DIABLO are indispensable for its function, and a seven-residue peptide derived from the amino terminus promotes procaspase-3 activation in vitro. Paper-8420924.
Expression of E93 in embryos is sufficient to induce cell death with many characteristics of apoptosis, but requires the H99 genetic interval that contains the rpr, hid and grim proapoptotic genes to induce nuclear changes diagnostic of apoptosis. Paper-8814113.
In Drosophila melanogaster, the pro-apoptotic proteins Reaper (Rpr), Grim and Hid ( head involution defective) all induce cell death by antagonizing the anti-apoptotic activity of Drosophila IAP1 ( DIAP1), thereby liberating caspases. Paper-9185308.
Here, we demonstrate, using gain-of-function and deletion alleles, that Drosophila Bruce (dBruce) can potently inhibit cell death induced by the essential Drosophila cell death activators Reaper (Rpr) and Grim but not Head involution defective ( Hid). Paper-9292033.
Both heterozygosity at the dronc locus and expression of dominant-negative DRONC mutants suppress the eye phenotype caused by reaper ( RPR) and head involution defective (HID), consistent with the idea that DRONC functions in the RPR and HID pathway. Paper-2133468.
Together, these data strongly suggest that IAP destabilization by Reaper in intact cells requires Reaper localization to mitochondria and that induction of IAP instability by Reaper is important for the potent induction of apoptosis in Drosophila cells. Paper-10040778.
Inhibitors of apoptosis proteins (IAPs) interact with caspases and inhibit their protease activity, whereas the IAP-inhibitory proteins Smac/ DIABLO in mammals and Reaper, Hid, and Grim in flies relieve IAP-mediated inhibition to induce cell death. Paper-9182101.
Taken together, these results strongly argue that drICE is an apoptotic caspase that acts downstream of rpr. drICE is therefore the first unequivocal link between the molecular machinery of Drosophila cell death and the conserved machinery of Caenorhabditis elegans and vertebrates. Paper-1046788.
Although gross development and lifespans were unaffected, we found that Debcl was required for pruning cells in the developing central nervous system. debcl genetically interacted with the ced-4/ Apaf1 counterpart dark, but was not required for killing by RHG ( Reaper, Hid, Grim) proteins. Paper-13553917.
Surprisingly, targeting DIAP1 to the endoplasmic reticulum instead of mitochondria is partially effective in allowing DeltaGH3 Reaper to promote DIAP1 degradation, suggesting that co-localization of DIAP and Reaper at a membrane surface is critical for the induction of DIAP degradation. Paper-12673938.
Collectively, these data provide a specific function for the GH3 domain in conferring protein-lipid interactions, demonstrate that both Reaper binding and mitochondrial localization are required for accelerated IAP degradation, and suggest that membrane localization per se contributes to DIAP1 auto-ubiquitination and degradation. Paper-12673938.
We show here that ecdysone-induced expression of the death activator genes reaper ( rpr) and head involution defective (hid) is required for destruction of the larval midgut and salivary glands during metamorphosis, with hid playing a primary role in the salivary glands and rpr and hid acting in a redundant manner in the midguts. Paper-10211153.
We show that cytoplasmic lysates made from S2 cells undergoing apoptosis induced by either reaper ( rpr) expression or cycloheximide treatment contain a caspase activity with DEVD specificity which can cleave p35, lamin DmO, drICE and DCP-1 in vitro, and which can trigger chromatin condensation in isolated nuclei. Paper-1236314.
Furthermore, protein kinase inhibitors H-7 (a PKC, PKA, PKG, MLCK, and CKI inhibitor), calphostin C (a PKC inhibitor), or H-89 (a PKA and PKG inhibitor) completely blocked apoptosis induced by rpr, suggesting that some kind of serine/ threonine protein kinase(s) act upstream of caspase in apoptotic pathway induced by rpr in S2 cells. Paper-8939064.
These synonyms are used for gene rpr (reaper): RPR, rp, Protein reaper, Dmel\CG4319, CG4319, Cell death protein rpr, anon-WO0162936.19.
These accession numbers are used for gene rpr: Q9VVP7 (UNIPROT__AC), Q4V3S2 (UNIPROT__AC), AAY55700 (NCBI_GENBANK__AC), AAA18983 (NCBI_GENBANK__AC).
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