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Caenorhabditis elegans NHR-14/HNF4α regulates DNA damage-induced apoptosis through cooperating with cep-1/p53

BACKGROUND: Nuclear hormone receptors are involved in transcriptional regulation and many important cellular processes including development and metabolism. However, its role in DNA damage-induced apoptosis remains elusive. METHODS: Synchronized young adult animals were irradiated with different dos...

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Autores principales: Sang, Lei, Dong, Rui, Liu, Rui, Hao, Qinggang, Bai, Weiyu, Sun, Jianwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9438139/
https://www.ncbi.nlm.nih.gov/pubmed/36050770
http://dx.doi.org/10.1186/s12964-022-00920-5
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author Sang, Lei
Dong, Rui
Liu, Rui
Hao, Qinggang
Bai, Weiyu
Sun, Jianwei
author_facet Sang, Lei
Dong, Rui
Liu, Rui
Hao, Qinggang
Bai, Weiyu
Sun, Jianwei
author_sort Sang, Lei
collection PubMed
description BACKGROUND: Nuclear hormone receptors are involved in transcriptional regulation and many important cellular processes including development and metabolism. However, its role in DNA damage-induced apoptosis remains elusive. METHODS: Synchronized young adult animals were irradiated with different doses of gamma-Ray, and then put back to culture at 20 °C. Germline cell apoptosis was scored at different time point. RESULTS: Deletion of nhr-14 led to decreased DNA damage-induced germline apoptosis, but not the physiological programmed cell death. We also demonstrate that nhr-14 functions downstream of the DNA damage checkpoint pathway. Moreover, we show that nhr-14 regulates egl-1 and ced-13 transcription upon DNA damage. Mechanistically, NHR-14 forms a complex with CEP-1/p53 and binds directly to the egl-1 promoter to promote egl-1 transcription.. CONCLUSIONS: Our results indicate that NHR-14/HNF4α cooperates with CEP-1/p53 to regulate DNA damage-induced apoptosis. GRAPHIC ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12964-022-00920-5.
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spelling pubmed-94381392022-09-03 Caenorhabditis elegans NHR-14/HNF4α regulates DNA damage-induced apoptosis through cooperating with cep-1/p53 Sang, Lei Dong, Rui Liu, Rui Hao, Qinggang Bai, Weiyu Sun, Jianwei Cell Commun Signal Research BACKGROUND: Nuclear hormone receptors are involved in transcriptional regulation and many important cellular processes including development and metabolism. However, its role in DNA damage-induced apoptosis remains elusive. METHODS: Synchronized young adult animals were irradiated with different doses of gamma-Ray, and then put back to culture at 20 °C. Germline cell apoptosis was scored at different time point. RESULTS: Deletion of nhr-14 led to decreased DNA damage-induced germline apoptosis, but not the physiological programmed cell death. We also demonstrate that nhr-14 functions downstream of the DNA damage checkpoint pathway. Moreover, we show that nhr-14 regulates egl-1 and ced-13 transcription upon DNA damage. Mechanistically, NHR-14 forms a complex with CEP-1/p53 and binds directly to the egl-1 promoter to promote egl-1 transcription.. CONCLUSIONS: Our results indicate that NHR-14/HNF4α cooperates with CEP-1/p53 to regulate DNA damage-induced apoptosis. GRAPHIC ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12964-022-00920-5. BioMed Central 2022-09-01 /pmc/articles/PMC9438139/ /pubmed/36050770 http://dx.doi.org/10.1186/s12964-022-00920-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Sang, Lei
Dong, Rui
Liu, Rui
Hao, Qinggang
Bai, Weiyu
Sun, Jianwei
Caenorhabditis elegans NHR-14/HNF4α regulates DNA damage-induced apoptosis through cooperating with cep-1/p53
title Caenorhabditis elegans NHR-14/HNF4α regulates DNA damage-induced apoptosis through cooperating with cep-1/p53
title_full Caenorhabditis elegans NHR-14/HNF4α regulates DNA damage-induced apoptosis through cooperating with cep-1/p53
title_fullStr Caenorhabditis elegans NHR-14/HNF4α regulates DNA damage-induced apoptosis through cooperating with cep-1/p53
title_full_unstemmed Caenorhabditis elegans NHR-14/HNF4α regulates DNA damage-induced apoptosis through cooperating with cep-1/p53
title_short Caenorhabditis elegans NHR-14/HNF4α regulates DNA damage-induced apoptosis through cooperating with cep-1/p53
title_sort caenorhabditis elegans nhr-14/hnf4α regulates dna damage-induced apoptosis through cooperating with cep-1/p53
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9438139/
https://www.ncbi.nlm.nih.gov/pubmed/36050770
http://dx.doi.org/10.1186/s12964-022-00920-5
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