A genetic screen for modifiers of <it>Drosophila </it>caspase Dcp-1 reveals caspase involvement in autophagy and novel caspase-related genes
<p>Abstract</p> <p>Background</p> <p>Caspases are cysteine proteases with essential functions in the apoptotic pathway; their proteolytic activity toward various substrates is associated with the morphological changes of cells. Recent reports have described non-apoptoti...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2010-01-01
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| Series: | BMC Cell Biology |
| Online Access: | http://www.biomedcentral.com/1471-2121/11/9 |
| _version_ | 1811334517433040896 |
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| author | Ahnn Joohong Heo Young-Shin Lee Judong Ryu Taewoo Kim Young-Il Lee Seung-Jae Yoo OokJoon |
| author_facet | Ahnn Joohong Heo Young-Shin Lee Judong Ryu Taewoo Kim Young-Il Lee Seung-Jae Yoo OokJoon |
| author_sort | Ahnn Joohong |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Caspases are cysteine proteases with essential functions in the apoptotic pathway; their proteolytic activity toward various substrates is associated with the morphological changes of cells. Recent reports have described non-apoptotic functions of caspases, including autophagy. In this report, we searched for novel modifiers of the phenotype of <it>Dcp-1 </it>gain-of-function (GF) animals by screening promoter element- inserted <it>Drosophila melanogaster </it>lines (EP lines).</p> <p>Results</p> <p>We screened ~15,000 EP lines and identified 72 <it>Dcp-1</it>-interacting genes that were classified into 10 groups based on their functions and pathways: 4 apoptosis signaling genes, 10 autophagy genes, 5 insulin/IGF and TOR signaling pathway genes, 6 MAP kinase and JNK signaling pathway genes, 4 ecdysone signaling genes, 6 ubiquitination genes, 11 various developmental signaling genes, 12 transcription factors, 3 translation factors, and 11 other unclassified genes including 5 functionally undefined genes. Among them, insulin/IGF and TOR signaling pathway, MAP kinase and JNK signaling pathway, and ecdysone signaling are known to be involved in autophagy. Together with the identification of autophagy genes, the results of our screen suggest that autophagy counteracts Dcp-1-induced apoptosis. Consistent with this idea, we show that expression of eGFP-Atg5 rescued the eye phenotype caused by <it>Dcp-1 </it>GF. Paradoxically, we found that over-expression of full-length <it>Dcp-1 </it>induced autophagy, as Atg8b-GFP, an indicator of autophagy, was increased in the eye imaginal discs and in the S2 cell line. Taken together, these data suggest that autophagy suppresses Dcp-1-mediated apoptotic cell death, whereas Dcp-1 positively regulates autophagy, possibly through feedback regulation.</p> <p>Conclusions</p> <p>We identified a number of <it>Dcp-1 </it>modifiers that genetically interact with Dcp-1-induced cell death. Our results showing that <it>Dcp-1 </it>and autophagy-related genes influence each other will aid future investigations of the complicated relationships between apoptosis and autophagy.</p> |
| first_indexed | 2024-04-13T17:10:15Z |
| format | Article |
| id | doaj.art-9b0746220c264b47b4e3e2aa0c0fc35d |
| institution | Directory Open Access Journal |
| issn | 1471-2121 |
| language | English |
| last_indexed | 2024-04-13T17:10:15Z |
| publishDate | 2010-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cell Biology |
| spelling | doaj.art-9b0746220c264b47b4e3e2aa0c0fc35d2022-12-22T02:38:19ZengBMCBMC Cell Biology1471-21212010-01-01111910.1186/1471-2121-11-9A genetic screen for modifiers of <it>Drosophila </it>caspase Dcp-1 reveals caspase involvement in autophagy and novel caspase-related genesAhnn JoohongHeo Young-ShinLee JudongRyu TaewooKim Young-IlLee Seung-JaeYoo OokJoon<p>Abstract</p> <p>Background</p> <p>Caspases are cysteine proteases with essential functions in the apoptotic pathway; their proteolytic activity toward various substrates is associated with the morphological changes of cells. Recent reports have described non-apoptotic functions of caspases, including autophagy. In this report, we searched for novel modifiers of the phenotype of <it>Dcp-1 </it>gain-of-function (GF) animals by screening promoter element- inserted <it>Drosophila melanogaster </it>lines (EP lines).</p> <p>Results</p> <p>We screened ~15,000 EP lines and identified 72 <it>Dcp-1</it>-interacting genes that were classified into 10 groups based on their functions and pathways: 4 apoptosis signaling genes, 10 autophagy genes, 5 insulin/IGF and TOR signaling pathway genes, 6 MAP kinase and JNK signaling pathway genes, 4 ecdysone signaling genes, 6 ubiquitination genes, 11 various developmental signaling genes, 12 transcription factors, 3 translation factors, and 11 other unclassified genes including 5 functionally undefined genes. Among them, insulin/IGF and TOR signaling pathway, MAP kinase and JNK signaling pathway, and ecdysone signaling are known to be involved in autophagy. Together with the identification of autophagy genes, the results of our screen suggest that autophagy counteracts Dcp-1-induced apoptosis. Consistent with this idea, we show that expression of eGFP-Atg5 rescued the eye phenotype caused by <it>Dcp-1 </it>GF. Paradoxically, we found that over-expression of full-length <it>Dcp-1 </it>induced autophagy, as Atg8b-GFP, an indicator of autophagy, was increased in the eye imaginal discs and in the S2 cell line. Taken together, these data suggest that autophagy suppresses Dcp-1-mediated apoptotic cell death, whereas Dcp-1 positively regulates autophagy, possibly through feedback regulation.</p> <p>Conclusions</p> <p>We identified a number of <it>Dcp-1 </it>modifiers that genetically interact with Dcp-1-induced cell death. Our results showing that <it>Dcp-1 </it>and autophagy-related genes influence each other will aid future investigations of the complicated relationships between apoptosis and autophagy.</p>http://www.biomedcentral.com/1471-2121/11/9 |
| spellingShingle | Ahnn Joohong Heo Young-Shin Lee Judong Ryu Taewoo Kim Young-Il Lee Seung-Jae Yoo OokJoon A genetic screen for modifiers of <it>Drosophila </it>caspase Dcp-1 reveals caspase involvement in autophagy and novel caspase-related genes BMC Cell Biology |
| title | A genetic screen for modifiers of <it>Drosophila </it>caspase Dcp-1 reveals caspase involvement in autophagy and novel caspase-related genes |
| title_full | A genetic screen for modifiers of <it>Drosophila </it>caspase Dcp-1 reveals caspase involvement in autophagy and novel caspase-related genes |
| title_fullStr | A genetic screen for modifiers of <it>Drosophila </it>caspase Dcp-1 reveals caspase involvement in autophagy and novel caspase-related genes |
| title_full_unstemmed | A genetic screen for modifiers of <it>Drosophila </it>caspase Dcp-1 reveals caspase involvement in autophagy and novel caspase-related genes |
| title_short | A genetic screen for modifiers of <it>Drosophila </it>caspase Dcp-1 reveals caspase involvement in autophagy and novel caspase-related genes |
| title_sort | genetic screen for modifiers of it drosophila it caspase dcp 1 reveals caspase involvement in autophagy and novel caspase related genes |
| url | http://www.biomedcentral.com/1471-2121/11/9 |
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