Steroid hormone control of cell death and cell survival: molecular insights using RNAi.
The insect steroid hormone ecdysone triggers programmed cell death of obsolete larval tissues during metamorphosis and provides a model system for understanding steroid hormone control of cell death and cell survival. Previous genome-wide expression studies of Drosophila larval salivary glands resul...
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| Language: | English |
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Public Library of Science (PLoS)
2009-02-01
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| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1000379&type=printable |
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| author | Suganthi Chittaranjan Melissa McConechy Ying-Chen Claire Hou J Douglas Freeman Lindsay Devorkin Sharon M Gorski |
| author_facet | Suganthi Chittaranjan Melissa McConechy Ying-Chen Claire Hou J Douglas Freeman Lindsay Devorkin Sharon M Gorski |
| author_sort | Suganthi Chittaranjan |
| collection | DOAJ |
| description | The insect steroid hormone ecdysone triggers programmed cell death of obsolete larval tissues during metamorphosis and provides a model system for understanding steroid hormone control of cell death and cell survival. Previous genome-wide expression studies of Drosophila larval salivary glands resulted in the identification of many genes associated with ecdysone-induced cell death and cell survival, but functional verification was lacking. In this study, we test functionally 460 of these genes using RNA interference in ecdysone-treated Drosophila l(2)mbn cells. Cell viability, cell morphology, cell proliferation, and apoptosis assays confirmed the effects of known genes and additionally resulted in the identification of six new pro-death related genes, including sorting nexin-like gene SH3PX1 and Sox box protein Sox14, and 18 new pro-survival genes. Identified genes were further characterized to determine their ecdysone dependency and potential function in cell death regulation. We found that the pro-survival function of five genes (Ras85D, Cp1, CG13784, CG32016, and CG33087), was dependent on ecdysone signaling. The TUNEL assay revealed an additional two genes (Kap-alpha3 and Smr) with an ecdysone-dependent cell survival function that was associated with reduced cell death. In vitro, Sox14 RNAi reduced the percentage of TUNEL-positive l(2)mbn cells (p<0.05) following ecdysone treatment, and Sox14 overexpression was sufficient to induce apoptosis. In vivo analyses of Sox14-RNAi animals revealed multiple phenotypes characteristic of aberrant or reduced ecdysone signaling, including defects in larval midgut and salivary gland destruction. These studies identify Sox14 as a positive regulator of ecdysone-mediated cell death and provide new insights into the molecular mechanisms underlying the ecdysone signaling network governing cell death and cell survival. |
| format | Article |
| id | doaj-art-9bda632a31ad42d38f789bcacfbcaff0 |
| institution | OA Journals |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2009-02-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS Genetics |
| spelling | doaj-art-9bda632a31ad42d38f789bcacfbcaff02025-08-20T02:17:24ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042009-02-0152e100037910.1371/journal.pgen.1000379Steroid hormone control of cell death and cell survival: molecular insights using RNAi.Suganthi ChittaranjanMelissa McConechyYing-Chen Claire HouJ Douglas FreemanLindsay DevorkinSharon M GorskiThe insect steroid hormone ecdysone triggers programmed cell death of obsolete larval tissues during metamorphosis and provides a model system for understanding steroid hormone control of cell death and cell survival. Previous genome-wide expression studies of Drosophila larval salivary glands resulted in the identification of many genes associated with ecdysone-induced cell death and cell survival, but functional verification was lacking. In this study, we test functionally 460 of these genes using RNA interference in ecdysone-treated Drosophila l(2)mbn cells. Cell viability, cell morphology, cell proliferation, and apoptosis assays confirmed the effects of known genes and additionally resulted in the identification of six new pro-death related genes, including sorting nexin-like gene SH3PX1 and Sox box protein Sox14, and 18 new pro-survival genes. Identified genes were further characterized to determine their ecdysone dependency and potential function in cell death regulation. We found that the pro-survival function of five genes (Ras85D, Cp1, CG13784, CG32016, and CG33087), was dependent on ecdysone signaling. The TUNEL assay revealed an additional two genes (Kap-alpha3 and Smr) with an ecdysone-dependent cell survival function that was associated with reduced cell death. In vitro, Sox14 RNAi reduced the percentage of TUNEL-positive l(2)mbn cells (p<0.05) following ecdysone treatment, and Sox14 overexpression was sufficient to induce apoptosis. In vivo analyses of Sox14-RNAi animals revealed multiple phenotypes characteristic of aberrant or reduced ecdysone signaling, including defects in larval midgut and salivary gland destruction. These studies identify Sox14 as a positive regulator of ecdysone-mediated cell death and provide new insights into the molecular mechanisms underlying the ecdysone signaling network governing cell death and cell survival.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1000379&type=printable |
| spellingShingle | Suganthi Chittaranjan Melissa McConechy Ying-Chen Claire Hou J Douglas Freeman Lindsay Devorkin Sharon M Gorski Steroid hormone control of cell death and cell survival: molecular insights using RNAi. PLoS Genetics |
| title | Steroid hormone control of cell death and cell survival: molecular insights using RNAi. |
| title_full | Steroid hormone control of cell death and cell survival: molecular insights using RNAi. |
| title_fullStr | Steroid hormone control of cell death and cell survival: molecular insights using RNAi. |
| title_full_unstemmed | Steroid hormone control of cell death and cell survival: molecular insights using RNAi. |
| title_short | Steroid hormone control of cell death and cell survival: molecular insights using RNAi. |
| title_sort | steroid hormone control of cell death and cell survival molecular insights using rnai |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1000379&type=printable |
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