The Experts below are selected from a list of 6060 Experts worldwide ranked by ideXlab platform
Sharon M. Gorski - One of the best experts on this subject based on the ideXlab platform.
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Hsp83 loss suppresses proteasomal activity resulting in an upregulation of Caspase-dependent compensatory autophagy
Autophagy, 2017Co-Authors: Courtney Choutka, Lindsay Devorkin, Ying-chen Claire Hou, Annie Moradian, Gregg B. Morin, Sharon M. GorskiAbstract:The 2 main degradative pathways that contribute to proteostasis are the ubiquitin-proteasome system and autophagy but how they are molecularly coordinated is not well understood. Here, we demonstrate an essential role for an Effector Caspase in the activation of compensatory autophagy when proteasomal activity is compromised. Functional loss of Hsp83, the Drosophila ortholog of human HSP90 (heat shock protein 90), resulted in reduced proteasomal activity and elevated levels of the Effector Caspase Dcp-1. Surprisingly, genetic analyses showed that the Caspase was not required for cell death in this context, but instead was essential for the ensuing compensatory autophagy, female fertility, and organism viability. The zymogen pro-Dcp-1 was found to interact with Hsp83 and undergo proteasomal regulation in an Hsp83-dependent manner. Our work not only reveals unappreciated roles for Hsp83 in proteasomal activity and regulation of Dcp-1, but identifies an Effector Caspase as a key regulatory factor for sustaining adaptation to cell stress in vivo.
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A mitochondrial-associated link between an Effector Caspase and autophagic flux.
Autophagy, 2014Co-Authors: Lindsay Devorkin, Sharon M. GorskiAbstract:It has become evident that Caspases function in nonapoptotic cellular processes in addition to the canonical role for Caspases in apoptotic cell death. We recently demonstrated that the Drosophila Effector Caspase Dcp-1 localizes to the mitochondria and positively regulates starvation-induced autophagic flux during mid-oogenesis. Loss of Dcp-1 leads to elongation of the mitochondrial network, increased levels of the adenine nucleotide translocase sesB, increased ATP levels, and a reduction in autophagy. We found that sesB is a negative regulator of autophagic flux, and Dcp-1 interacts with sesB in a nonproteolytic manner to regulate its stability, uncovering a novel mechanism of mitochondrial associated, Caspase-mediated regulation of autophagy in vivo.
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The Drosophila Effector Caspase Dcp-1 regulates mitochondrial dynamics and autophagic flux via SesB
The Journal of cell biology, 2014Co-Authors: Lindsay Devorkin, Ying-chen Claire Hou, Annie Moradian, Gregg B. Morin, Sharon M. GorskiAbstract:Increasing evidence reveals that a subset of proteins participates in both the autophagy and apoptosis pathways, and this intersection is important in normal physiological contexts and in pathological settings. In this paper, we show that the Drosophila Effector Caspase, Drosophila Caspase 1 (Dcp-1), localizes within mitochondria and regulates mitochondrial morphology and autophagic flux. Loss of Dcp-1 led to mitochondrial elongation, increased levels of the mitochondrial adenine nucleotide translocase stress-sensitive B (SesB), increased adenosine triphosphate (ATP), and a reduction in autophagic flux. Moreover, we find that SesB suppresses autophagic flux during midoogenesis, identifying a novel negative regulator of autophagy. Reduced SesB activity or depletion of ATP by oligomycin A could rescue the autophagic defect in Dcp-1 loss-of-function flies, demonstrating that Dcp-1 promotes autophagy by negatively regulating SesB and ATP levels. Furthermore, we find that pro-Dcp-1 interacts with SesB in a nonproteolytic manner to regulate its stability. These data reveal a new mitochondrial-associated molecular link between nonapoptotic Caspase function and autophagy regulation in vivo.
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Effector Caspase dcp 1 and iap protein bruce regulate starvation induced autophagy during drosophila melanogaster oogenesis
Journal of Cell Biology, 2008Co-Authors: Ying-chen Claire Hou, Suganthi Chittaranjan, Sharon González Barbosa, Kimberly Mccall, Sharon M. GorskiAbstract:Canadian Institutes of Health (MOP-78882); National Institutes of Health (R01 GM60574); Summer Undergraduate Research Fellowship program at Boston University; National Science Foundation (0450339)
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Effector Caspase Dcp-1 and IAP protein Bruce regulate starvation-induced autophagy during Drosophila melanogaster oogenesis
The Journal of cell biology, 2008Co-Authors: Ying-chen Claire Hou, Suganthi Chittaranjan, Sharon González Barbosa, Kimberly Mccall, Sharon M. GorskiAbstract:A complex relationship exists between autophagy and apoptosis, but the regulatory mechanisms underlying their interactions are largely unknown. We conducted a systematic study of Drosophila melanogaster cell death-related genes to determine their requirement in the regulation of starvation-induced autophagy. We discovered that six cell death genes--death Caspase-1 (Dcp-1), hid, Bruce, Buffy, debcl, and p53-as well as Ras-Raf-mitogen activated protein kinase signaling pathway components had a role in autophagy regulation in D. melanogaster cultured cells. During D. melanogaster oogenesis, we found that autophagy is induced at two nutrient status checkpoints: germarium and mid-oogenesis. At these two stages, the Effector Caspase Dcp-1 and the inhibitor of apoptosis protein Bruce function to regulate both autophagy and starvation-induced cell death. Mutations in Atg1 and Atg7 resulted in reduced DNA fragmentation in degenerating midstage egg chambers but did not appear to affect nuclear condensation, which indicates that autophagy contributes in part to cell death in the ovary. Our study provides new insights into the molecular mechanisms that coordinately regulate autophagic and apoptotic events in vivo.
Andrew J Fisher - One of the best experts on this subject based on the ideXlab platform.
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Crystal structure of an invertebrate Caspase.
The Journal of biological chemistry, 2003Co-Authors: Charles M. Forsyth, Donna Lemongello, Paul D Friesen, D J Lacount, Andrew J FisherAbstract:Caspases play an essential role in the execution of apoptosis. These cysteine proteases are highly conserved among metazoans and are translated as inactive zymogens, which are activated by proteolytic cleavages to generate the large and small subunits and remove the N-terminal prodomain. The 2.3 A resolution crystal structure of active Sf-Caspase-1, the principal Effector Caspase of the insect Spodoptera frugiperda, is presented here. The structure represents the first nonhuman Caspase to be resolved. The structure of the cleaved and active protease was determined with the tetrapeptide inhibitor N-acetyl-Asp-Glu-Val-Asp-chloromethylketone covalently bonded to the active site cysteine. As expected, the overall fold of Sf-Caspase-1 is exceedingly similar to that of the five active Caspases from humans solved to date. The overall structure and active site arrangement of Sf-Caspase-1 is most comparable with that of the human Effector Caspases, with which it shares highest sequence homology. The most prominent structural difference with Sf-Caspase-1 is the position of the N-terminal region of the large subunit. Unlike the N terminus of human Caspases, the N terminus of Sf-Caspase-1 originates from the active site side where it interacts with active site loop L2 and then extends to the backside of the heterodimer. This unusual structural arrangement raises the possibility that the N-terminal prodomain plays a regulatory role during Effector Caspase activation or enzyme activity in insects.
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crystallization and low resolution structure of an Effector Caspase p35 complex similarities and differences to an initiator Caspase p35 complex
Acta Crystallographica Section D-biological Crystallography, 2002Co-Authors: Michael J Eddins, Donna Lemongello, Paul D Friesen, Andrew J FisherAbstract:The aspartate-specific Caspases play a pivotal role in the execution of programmed cell death and therefore constitute important targets for the control of apoptosis. Upon ectopic expression, baculovirus P35 inhibits apoptosis in phylogenetically diverse organisms by suppressing the proteolytic activity of the cellular Caspases in a cleavage-dependent mechanism. After cleavage by Caspase, the P35 fragments remain bound to the target Caspase, forming an inhibitory complex that sequesters the Caspase from further activity. Crystals of a complex between P35 and Sf-Caspase-1, an insect Effector-Caspase, were grown. A 5.2 A resolution structure of this inhibitory complex was determined by molecular-replacement methods. The structure reveals few regions of interaction between the two proteins, much like that observed in the structure of the recently solved human initiator-Caspase/P35 complex. In the Effector-Caspase/P35 complex structure presented here, the P35 molecule shifts towards a loop that is conserved in Effector Caspases but absent in initiator Caspase. This shift could strengthen interactions between the two proteins and may explain the preference of P35 for inhibiting Effector-Caspases.
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Crystallization and low-resolution structure of an Effector-Caspase/P35 complex: similarities and differences to an initiator-Caspase/P35 complex.
Acta crystallographica. Section D Biological crystallography, 2002Co-Authors: Michael J Eddins, Donna Lemongello, Paul D Friesen, Andrew J FisherAbstract:The aspartate-specific Caspases play a pivotal role in the execution of programmed cell death and therefore constitute important targets for the control of apoptosis. Upon ectopic expression, baculovirus P35 inhibits apoptosis in phylogenetically diverse organisms by suppressing the proteolytic activity of the cellular Caspases in a cleavage-dependent mechanism. After cleavage by Caspase, the P35 fragments remain bound to the target Caspase, forming an inhibitory complex that sequesters the Caspase from further activity. Crystals of a complex between P35 and Sf-Caspase-1, an insect Effector-Caspase, were grown. A 5.2 A resolution structure of this inhibitory complex was determined by molecular-replacement methods. The structure reveals few regions of interaction between the two proteins, much like that observed in the structure of the recently solved human initiator-Caspase/P35 complex. In the Effector-Caspase/P35 complex structure presented here, the P35 molecule shifts towards a loop that is conserved in Effector Caspases but absent in initiator Caspase. This shift could strengthen interactions between the two proteins and may explain the preference of P35 for inhibiting Effector-Caspases.
Timothy W. Flegel - One of the best experts on this subject based on the ideXlab platform.
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Interaction study of a novel Macrobrachium rosenbergii Effector Caspase with B2 and capsid proteins of M. rosenbergii nodavirus reveals their roles in apoptosis
Fish & shellfish immunology, 2015Co-Authors: Supak Youngcharoen, Tareerat Lertwimol, Saengchan Senapin, Timothy W. Flegel, Siwaporn Longyant, Paisarn Sithigorngul, Parin ChaivisuthangkuraAbstract:Apoptosis is an essential immune response to protect invertebrates from virus infected cells. In shrimp, virus infection has been reported to induce apoptosis. Macrobrachium rosenbergii (Mr) was considered to be a disease-resistant host when compared to penaeid shrimps. Caspase-3 was classified as an executioner Caspase which played a key role in virus-induced apoptosis. In this study, an Effector Caspase gene of M. rosenbergii (Mrcasp) was cloned and characterized. The open reading frame (ORF) of Mrcasp was 957 nucleotide encoding 318 amino acid with a deduced molecular mass of 35.87 kDa. RT-PCR analysis showed the presence of Mrcasp in all examined tissues. The phylogenetic tree indicated that Mrcasp was closely related with Caspase 3 of shrimp. The functions of the Mrcasp, B2 and capsid proteins of M. rosenbergii nodavirus (MrNV) were assayed in Sf-9 cells. The results showed that Mrcasp induce apoptotic morphology cells; however, capsid protein of MrNV could inhibit apoptotic cells whereas B2 could neither induce nor inhibit apoptotic cells by DAPI staining. The protein interaction between Mrcasp and viral MrNV structure revealed that Mrcasp did not bind to B2 or capsid protein whereas B2 and capsid proteins could bind directly to each other. This study reported a novel sequence of a full-length Mrcasp and its functional studies indicated that Mrcasp could induce apoptotic cells. Our data is the first report demonstrating the direct protein-protein interaction between capsid protein and B2 protein of MrNV.
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Two new anti-apoptotic proteins of white spot syndrome virus that bind to an Effector Caspase (PmCasp) of the giant tiger shrimp Penaeus (Penaeus) monodon.
Fish & shellfish immunology, 2014Co-Authors: Tareerat Lertwimol, Pakkakul Sangsuriya, Kornsunee Phiwsaiya, Saengchan Senapin, Amornrat Phongdara, Chuenchit Boonchird, Timothy W. FlegelAbstract:White spot syndrome virus proteins WSSV134 and WSSV322 have been shown to bind with the p20 domain (residues 55-214) of Penaeus monodon Caspase (PmCasp) protein through yeast two-hybrid screening. Binding was confirmed for the p20 domain and the full-length Caspase by co-immunoprecipitation. WSSV134 is also known as the WSSV structural protein VP36A, but no function or conserved domains have been ascribed to WSSV322. Discovery of the Caspase binding activity of these two proteins led to an investigation of their possible anti-apoptotic roles. Full-length PmCasp was confirmed to be an Effector Caspase by inducing apoptosis in transfected Sf-9 cells as assessed by DAPI staining. Using the same cell model, comparison of cells co-transfected with PmCasp and either WSSV134 or WSSV322 revealed that both of the binding proteins had anti-apoptotic activity. However, using the same Sf-9 protocol with anti-apoptosis protein-1 (AAP-1; also called WSSV449) previously shown to bind and inactivate a different Effector Caspase from P. monodon (Pm Caspase) did not block apoptosis induced by PmCasp. The results revealed diversity in Effector Caspases and their viral protein inhibitors in P. monodon.
Paul D Friesen - One of the best experts on this subject based on the ideXlab platform.
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Baculovirus Caspase inhibitors P49 and P35 block virus-induced apoptosis downstream of Effector Caspase DrICE activation in Drosophila melanogaster cells.
Journal of virology, 2007Co-Authors: Erica A. Lannan, Rianna Vandergaast, Paul D FriesenAbstract:Baculoviruses induce widespread apoptosis in invertebrates. To better understand the pathways by which these DNA viruses trigger apoptosis, we have used a combination of RNA silencing and overexpression of viral and host apoptotic regulators to identify cell death components in the model system of Drosophila melanogaster. Here we report that the principal Effector Caspase DrICE is required for baculovirus-induced apoptosis of Drosophila DL-1 cells as demonstrated by RNA silencing. proDrICE was proteolytically cleaved and activated during infection. Activation was blocked by overexpression of the cellular inhibitor-of-apoptosis proteins DIAP1 and SfIAP but not by the baculovirus Caspase inhibitor P49 or P35. Rather, the substrate inhibitors P49 and P35 prevented virus-induced apoptosis by arresting active DrICE through formation of stable inhibitory complexes. Consistent with a two-step activation mechanism, proDrICE was cleaved at the large/small subunit junction TETD230-G by a DIAP1-inhibitable, P49/P35-resistant protease and then at the prodomain junction DHTD28-A by a P49/P35-sensitive protease. Confirming that P49 targeted DrICE and not the initiator Caspase DRONC, depletion of DrICE by RNA silencing suppressed virus-induced cleavage of P49. Collectively, our findings indicate that whereas DIAP1 functions upstream to block DrICE activation, P49 and P35 act downstream by inhibiting active DrICE. Given that P49 has the potential to inhibit both upstream initiator Caspases and downstream Effector Caspases, we conclude that P49 is a broad-spectrum Caspase inhibitor that likely provides a selective advantage to baculoviruses in different cellular backgrounds.
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Crystal structure of an invertebrate Caspase.
The Journal of biological chemistry, 2003Co-Authors: Charles M. Forsyth, Donna Lemongello, Paul D Friesen, D J Lacount, Andrew J FisherAbstract:Caspases play an essential role in the execution of apoptosis. These cysteine proteases are highly conserved among metazoans and are translated as inactive zymogens, which are activated by proteolytic cleavages to generate the large and small subunits and remove the N-terminal prodomain. The 2.3 A resolution crystal structure of active Sf-Caspase-1, the principal Effector Caspase of the insect Spodoptera frugiperda, is presented here. The structure represents the first nonhuman Caspase to be resolved. The structure of the cleaved and active protease was determined with the tetrapeptide inhibitor N-acetyl-Asp-Glu-Val-Asp-chloromethylketone covalently bonded to the active site cysteine. As expected, the overall fold of Sf-Caspase-1 is exceedingly similar to that of the five active Caspases from humans solved to date. The overall structure and active site arrangement of Sf-Caspase-1 is most comparable with that of the human Effector Caspases, with which it shares highest sequence homology. The most prominent structural difference with Sf-Caspase-1 is the position of the N-terminal region of the large subunit. Unlike the N terminus of human Caspases, the N terminus of Sf-Caspase-1 originates from the active site side where it interacts with active site loop L2 and then extends to the backside of the heterodimer. This unusual structural arrangement raises the possibility that the N-terminal prodomain plays a regulatory role during Effector Caspase activation or enzyme activity in insects.
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crystallization and low resolution structure of an Effector Caspase p35 complex similarities and differences to an initiator Caspase p35 complex
Acta Crystallographica Section D-biological Crystallography, 2002Co-Authors: Michael J Eddins, Donna Lemongello, Paul D Friesen, Andrew J FisherAbstract:The aspartate-specific Caspases play a pivotal role in the execution of programmed cell death and therefore constitute important targets for the control of apoptosis. Upon ectopic expression, baculovirus P35 inhibits apoptosis in phylogenetically diverse organisms by suppressing the proteolytic activity of the cellular Caspases in a cleavage-dependent mechanism. After cleavage by Caspase, the P35 fragments remain bound to the target Caspase, forming an inhibitory complex that sequesters the Caspase from further activity. Crystals of a complex between P35 and Sf-Caspase-1, an insect Effector-Caspase, were grown. A 5.2 A resolution structure of this inhibitory complex was determined by molecular-replacement methods. The structure reveals few regions of interaction between the two proteins, much like that observed in the structure of the recently solved human initiator-Caspase/P35 complex. In the Effector-Caspase/P35 complex structure presented here, the P35 molecule shifts towards a loop that is conserved in Effector Caspases but absent in initiator Caspase. This shift could strengthen interactions between the two proteins and may explain the preference of P35 for inhibiting Effector-Caspases.
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Crystallization and low-resolution structure of an Effector-Caspase/P35 complex: similarities and differences to an initiator-Caspase/P35 complex.
Acta crystallographica. Section D Biological crystallography, 2002Co-Authors: Michael J Eddins, Donna Lemongello, Paul D Friesen, Andrew J FisherAbstract:The aspartate-specific Caspases play a pivotal role in the execution of programmed cell death and therefore constitute important targets for the control of apoptosis. Upon ectopic expression, baculovirus P35 inhibits apoptosis in phylogenetically diverse organisms by suppressing the proteolytic activity of the cellular Caspases in a cleavage-dependent mechanism. After cleavage by Caspase, the P35 fragments remain bound to the target Caspase, forming an inhibitory complex that sequesters the Caspase from further activity. Crystals of a complex between P35 and Sf-Caspase-1, an insect Effector-Caspase, were grown. A 5.2 A resolution structure of this inhibitory complex was determined by molecular-replacement methods. The structure reveals few regions of interaction between the two proteins, much like that observed in the structure of the recently solved human initiator-Caspase/P35 complex. In the Effector-Caspase/P35 complex structure presented here, the P35 molecule shifts towards a loop that is conserved in Effector Caspases but absent in initiator Caspase. This shift could strengthen interactions between the two proteins and may explain the preference of P35 for inhibiting Effector-Caspases.
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Caspase Inhibitor P35 and Inhibitor of Apoptosis Op-IAP Block in Vivo Proteolytic Activation of an Effector Caspase at Different Steps
The Journal of biological chemistry, 2000Co-Authors: D J Lacount, S. F. Hanson, Christine L. Schneider, Paul D FriesenAbstract:Signal-induced activation of Caspases, the critical protease Effectors of apoptosis, requires proteolytic processing of their inactive proenzymes. Consequently, regulation of proCaspase processing is critical to apoptotic execution. We report here that baculovirus panCaspase inhibitor P35 and inhibitor of apoptosis Op-IAP prevent Caspase activation in vivo, but at different steps. By monitoring proteolytic processing of endogenous Sf-Caspase-1, an insect group II Effector Caspase, we show that Op-IAP blocked the first activation cleavage at TETD downward arrowG between the large and small Caspase subunits. In contrast, P35 failed to affect this cleavage, but functioned downstream to block maturation cleavages (DXXD downward arrow(G/A)) of the large subunit. Substitution of P35's reactive site residues with TETDG failed to increase its effectiveness for blocking TETD downward arrowG processing of pro-Sf-Caspase-1, despite wild-type function for suppressing apoptosis. These data are consistent with the involvement of a novel initiator Caspase that is resistant to P35, but directly or indirectly inhibitable by Op-IAP. The conservation of TETD downward arrowG processing sites among insect Effector Caspases, including Drosophila drICE and DCP-1, suggests that in vivo activation of these group II Caspases involves a P35-insensitive Caspase and supports a model wherein apical and Effector Caspases function through a proteolytic cascade to execute apoptosis in insects.
Ying-chen Claire Hou - One of the best experts on this subject based on the ideXlab platform.
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Hsp83 loss suppresses proteasomal activity resulting in an upregulation of Caspase-dependent compensatory autophagy
Autophagy, 2017Co-Authors: Courtney Choutka, Lindsay Devorkin, Ying-chen Claire Hou, Annie Moradian, Gregg B. Morin, Sharon M. GorskiAbstract:The 2 main degradative pathways that contribute to proteostasis are the ubiquitin-proteasome system and autophagy but how they are molecularly coordinated is not well understood. Here, we demonstrate an essential role for an Effector Caspase in the activation of compensatory autophagy when proteasomal activity is compromised. Functional loss of Hsp83, the Drosophila ortholog of human HSP90 (heat shock protein 90), resulted in reduced proteasomal activity and elevated levels of the Effector Caspase Dcp-1. Surprisingly, genetic analyses showed that the Caspase was not required for cell death in this context, but instead was essential for the ensuing compensatory autophagy, female fertility, and organism viability. The zymogen pro-Dcp-1 was found to interact with Hsp83 and undergo proteasomal regulation in an Hsp83-dependent manner. Our work not only reveals unappreciated roles for Hsp83 in proteasomal activity and regulation of Dcp-1, but identifies an Effector Caspase as a key regulatory factor for sustaining adaptation to cell stress in vivo.
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The Drosophila Effector Caspase Dcp-1 regulates mitochondrial dynamics and autophagic flux via SesB
The Journal of cell biology, 2014Co-Authors: Lindsay Devorkin, Ying-chen Claire Hou, Annie Moradian, Gregg B. Morin, Sharon M. GorskiAbstract:Increasing evidence reveals that a subset of proteins participates in both the autophagy and apoptosis pathways, and this intersection is important in normal physiological contexts and in pathological settings. In this paper, we show that the Drosophila Effector Caspase, Drosophila Caspase 1 (Dcp-1), localizes within mitochondria and regulates mitochondrial morphology and autophagic flux. Loss of Dcp-1 led to mitochondrial elongation, increased levels of the mitochondrial adenine nucleotide translocase stress-sensitive B (SesB), increased adenosine triphosphate (ATP), and a reduction in autophagic flux. Moreover, we find that SesB suppresses autophagic flux during midoogenesis, identifying a novel negative regulator of autophagy. Reduced SesB activity or depletion of ATP by oligomycin A could rescue the autophagic defect in Dcp-1 loss-of-function flies, demonstrating that Dcp-1 promotes autophagy by negatively regulating SesB and ATP levels. Furthermore, we find that pro-Dcp-1 interacts with SesB in a nonproteolytic manner to regulate its stability. These data reveal a new mitochondrial-associated molecular link between nonapoptotic Caspase function and autophagy regulation in vivo.
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Effector Caspase dcp 1 and iap protein bruce regulate starvation induced autophagy during drosophila melanogaster oogenesis
Journal of Cell Biology, 2008Co-Authors: Ying-chen Claire Hou, Suganthi Chittaranjan, Sharon González Barbosa, Kimberly Mccall, Sharon M. GorskiAbstract:Canadian Institutes of Health (MOP-78882); National Institutes of Health (R01 GM60574); Summer Undergraduate Research Fellowship program at Boston University; National Science Foundation (0450339)
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Effector Caspase Dcp-1 and IAP protein Bruce regulate starvation-induced autophagy during Drosophila melanogaster oogenesis
The Journal of cell biology, 2008Co-Authors: Ying-chen Claire Hou, Suganthi Chittaranjan, Sharon González Barbosa, Kimberly Mccall, Sharon M. GorskiAbstract:A complex relationship exists between autophagy and apoptosis, but the regulatory mechanisms underlying their interactions are largely unknown. We conducted a systematic study of Drosophila melanogaster cell death-related genes to determine their requirement in the regulation of starvation-induced autophagy. We discovered that six cell death genes--death Caspase-1 (Dcp-1), hid, Bruce, Buffy, debcl, and p53-as well as Ras-Raf-mitogen activated protein kinase signaling pathway components had a role in autophagy regulation in D. melanogaster cultured cells. During D. melanogaster oogenesis, we found that autophagy is induced at two nutrient status checkpoints: germarium and mid-oogenesis. At these two stages, the Effector Caspase Dcp-1 and the inhibitor of apoptosis protein Bruce function to regulate both autophagy and starvation-induced cell death. Mutations in Atg1 and Atg7 resulted in reduced DNA fragmentation in degenerating midstage egg chambers but did not appear to affect nuclear condensation, which indicates that autophagy contributes in part to cell death in the ovary. Our study provides new insights into the molecular mechanisms that coordinately regulate autophagic and apoptotic events in vivo.
