Evidence for existence of an apoptosis‐inducing BH3‐only protein, sayonara, in Drosophila
Cells need to sense stresses to initiate the execution of the dormant cell death program. Since the discovery of the first BH3‐only protein Bad, BH3‐only proteins have been recognized as indispensable stress sensors that induce apoptosis. BH3‐only proteins have so far not been identified in Drosophi...
| Main Authors: | , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group UK
2024
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| Online Access: | https://hdl.handle.net/1721.1/157496 |
| _version_ | 1824458169811730432 |
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| author | Ikegawa, Yuko Combet, Christophe Groussin, Mathieu Navratil, Vincent Safar‐Remali, Sabrina Shiota, Takuya Aouacheria, Abdel Yoo, Sa K. |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Ikegawa, Yuko Combet, Christophe Groussin, Mathieu Navratil, Vincent Safar‐Remali, Sabrina Shiota, Takuya Aouacheria, Abdel Yoo, Sa K. |
| author_sort | Ikegawa, Yuko |
| collection | MIT |
| description | Cells need to sense stresses to initiate the execution of the dormant cell death program. Since the discovery of the first BH3‐only protein Bad, BH3‐only proteins have been recognized as indispensable stress sensors that induce apoptosis. BH3‐only proteins have so far not been identified in Drosophila despite their importance in other organisms. Here, we identify the first Drosophila BH3‐only protein and name it sayonara. Sayonara induces apoptosis in a BH3 motif‐dependent manner and interacts genetically and biochemically with the BCL‐2 homologous proteins, Buffy and Debcl. There is a positive feedback loop between Sayonara‐mediated caspase activation and autophagy. The BH3 motif of sayonara phylogenetically appeared at the time of the ancestral gene duplication that led to the formation of Buffy and Debcl in the dipteran lineage. To our knowledge, this is the first identification of a bona fide BH3‐only protein in Drosophila, thus providing a unique example of how cell death mechanisms can evolve both through time and across taxa. |
| first_indexed | 2025-02-19T04:21:37Z |
| format | Article |
| id | mit-1721.1/157496 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2025-02-19T04:21:37Z |
| publishDate | 2024 |
| publisher | Nature Publishing Group UK |
| record_format | dspace |
| spelling | mit-1721.1/1574962025-01-05T04:46:25Z Evidence for existence of an apoptosis‐inducing BH3‐only protein, sayonara, in Drosophila Ikegawa, Yuko Combet, Christophe Groussin, Mathieu Navratil, Vincent Safar‐Remali, Sabrina Shiota, Takuya Aouacheria, Abdel Yoo, Sa K. Massachusetts Institute of Technology. Department of Biological Engineering Cells need to sense stresses to initiate the execution of the dormant cell death program. Since the discovery of the first BH3‐only protein Bad, BH3‐only proteins have been recognized as indispensable stress sensors that induce apoptosis. BH3‐only proteins have so far not been identified in Drosophila despite their importance in other organisms. Here, we identify the first Drosophila BH3‐only protein and name it sayonara. Sayonara induces apoptosis in a BH3 motif‐dependent manner and interacts genetically and biochemically with the BCL‐2 homologous proteins, Buffy and Debcl. There is a positive feedback loop between Sayonara‐mediated caspase activation and autophagy. The BH3 motif of sayonara phylogenetically appeared at the time of the ancestral gene duplication that led to the formation of Buffy and Debcl in the dipteran lineage. To our knowledge, this is the first identification of a bona fide BH3‐only protein in Drosophila, thus providing a unique example of how cell death mechanisms can evolve both through time and across taxa. 2024-11-05T19:51:39Z 2024-11-05T19:51:39Z 2023-02-02 2024-10-27T17:20:39Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/157496 The EMBO Journal. 2023 Feb 02;42(8):EMBJ2021110454 en https://doi.org/10.15252/embj.2021110454 The EMBO Journal Creative Commons Attribution https://creativecommons.org/licenses/by/4.0/ The Author(s) application/pdf Nature Publishing Group UK Nature Publishing Group UK |
| spellingShingle | Ikegawa, Yuko Combet, Christophe Groussin, Mathieu Navratil, Vincent Safar‐Remali, Sabrina Shiota, Takuya Aouacheria, Abdel Yoo, Sa K. Evidence for existence of an apoptosis‐inducing BH3‐only protein, sayonara, in Drosophila |
| title | Evidence for existence of an apoptosis‐inducing BH3‐only protein, sayonara, in Drosophila |
| title_full | Evidence for existence of an apoptosis‐inducing BH3‐only protein, sayonara, in Drosophila |
| title_fullStr | Evidence for existence of an apoptosis‐inducing BH3‐only protein, sayonara, in Drosophila |
| title_full_unstemmed | Evidence for existence of an apoptosis‐inducing BH3‐only protein, sayonara, in Drosophila |
| title_short | Evidence for existence of an apoptosis‐inducing BH3‐only protein, sayonara, in Drosophila |
| title_sort | evidence for existence of an apoptosis inducing bh3 only protein sayonara in drosophila |
| url | https://hdl.handle.net/1721.1/157496 |
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