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Snail modulates JNK-mediated cell death in Drosophila

Cell death plays a pivotal role in animal development and tissue homeostasis. Dysregulation of this process is associated with a wide variety of human diseases, including developmental and immunological disorders, neurodegenerative diseases and tumors. While the fundamental role of JNK pathway in ce...

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Autores principales: Wu, Chenxi, Li, Zhuojie, Ding, Xiang, Guo, Xiaowei, Sun, Ying, Wang, Xingjun, Hu, Yujia, Li, Tongtong, La, Xiaojin, Li, Jianing, Li, Ji-an, Li, Wenzhe, Xue, Lei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879600/
https://www.ncbi.nlm.nih.gov/pubmed/31772150
http://dx.doi.org/10.1038/s41419-019-2135-7
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author Wu, Chenxi
Li, Zhuojie
Ding, Xiang
Guo, Xiaowei
Sun, Ying
Wang, Xingjun
Hu, Yujia
Li, Tongtong
La, Xiaojin
Li, Jianing
Li, Ji-an
Li, Wenzhe
Xue, Lei
author_facet Wu, Chenxi
Li, Zhuojie
Ding, Xiang
Guo, Xiaowei
Sun, Ying
Wang, Xingjun
Hu, Yujia
Li, Tongtong
La, Xiaojin
Li, Jianing
Li, Ji-an
Li, Wenzhe
Xue, Lei
author_sort Wu, Chenxi
collection PubMed
description Cell death plays a pivotal role in animal development and tissue homeostasis. Dysregulation of this process is associated with a wide variety of human diseases, including developmental and immunological disorders, neurodegenerative diseases and tumors. While the fundamental role of JNK pathway in cell death has been extensively studied, its down-stream regulators and the underlying mechanisms remain largely elusive. From a Drosophila genetic screen, we identified Snail (Sna), a Zinc-finger transcription factor, as a novel modulator of ectopic Egr-induced JNK-mediated cell death. In addition, sna is essential for the physiological function of JNK signaling in development. Our genetic epistasis data suggest that Sna acts downstream of JNK to promote cell death. Mechanistically, JNK signaling triggers dFoxO-dependent transcriptional activation of sna. Thus, our findings not only reveal a novel function and the underlying mechanism of Sna in modulating JNK-mediated cell death, but also provide a potential drug target and therapeutic strategies for JNK signaling-related diseases.
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spelling pubmed-68796002019-11-29 Snail modulates JNK-mediated cell death in Drosophila Wu, Chenxi Li, Zhuojie Ding, Xiang Guo, Xiaowei Sun, Ying Wang, Xingjun Hu, Yujia Li, Tongtong La, Xiaojin Li, Jianing Li, Ji-an Li, Wenzhe Xue, Lei Cell Death Dis Article Cell death plays a pivotal role in animal development and tissue homeostasis. Dysregulation of this process is associated with a wide variety of human diseases, including developmental and immunological disorders, neurodegenerative diseases and tumors. While the fundamental role of JNK pathway in cell death has been extensively studied, its down-stream regulators and the underlying mechanisms remain largely elusive. From a Drosophila genetic screen, we identified Snail (Sna), a Zinc-finger transcription factor, as a novel modulator of ectopic Egr-induced JNK-mediated cell death. In addition, sna is essential for the physiological function of JNK signaling in development. Our genetic epistasis data suggest that Sna acts downstream of JNK to promote cell death. Mechanistically, JNK signaling triggers dFoxO-dependent transcriptional activation of sna. Thus, our findings not only reveal a novel function and the underlying mechanism of Sna in modulating JNK-mediated cell death, but also provide a potential drug target and therapeutic strategies for JNK signaling-related diseases. Nature Publishing Group UK 2019-11-26 /pmc/articles/PMC6879600/ /pubmed/31772150 http://dx.doi.org/10.1038/s41419-019-2135-7 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Wu, Chenxi
Li, Zhuojie
Ding, Xiang
Guo, Xiaowei
Sun, Ying
Wang, Xingjun
Hu, Yujia
Li, Tongtong
La, Xiaojin
Li, Jianing
Li, Ji-an
Li, Wenzhe
Xue, Lei
Snail modulates JNK-mediated cell death in Drosophila
title Snail modulates JNK-mediated cell death in Drosophila
title_full Snail modulates JNK-mediated cell death in Drosophila
title_fullStr Snail modulates JNK-mediated cell death in Drosophila
title_full_unstemmed Snail modulates JNK-mediated cell death in Drosophila
title_short Snail modulates JNK-mediated cell death in Drosophila
title_sort snail modulates jnk-mediated cell death in drosophila
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879600/
https://www.ncbi.nlm.nih.gov/pubmed/31772150
http://dx.doi.org/10.1038/s41419-019-2135-7
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