Cargando…

p53 induces ARTS to promote mitochondrial apoptosis

Apoptosis related protein in TGF-β signaling pathway (ARTS) was originally discovered in cells undergoing apoptosis in response to TGF-β, but ARTS also acts downstream of many other apoptotic stimuli. ARTS induces apoptosis by antagonizing the anti-apoptotic proteins XIAP and Bcl-2. Here we identifi...

Descripción completa

Detalles Bibliográficos
Autores principales: Hao, Qian, Chen, Jiaxiang, Liao, Junming, Huang, Yingdan, Gan, Yu, Larisch, Sarit, Zeng, Shelya X., Lu, Hua, Zhou, Xiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904775/
https://www.ncbi.nlm.nih.gov/pubmed/33627621
http://dx.doi.org/10.1038/s41419-021-03463-8
_version_ 1783654985052979200
author Hao, Qian
Chen, Jiaxiang
Liao, Junming
Huang, Yingdan
Gan, Yu
Larisch, Sarit
Zeng, Shelya X.
Lu, Hua
Zhou, Xiang
author_facet Hao, Qian
Chen, Jiaxiang
Liao, Junming
Huang, Yingdan
Gan, Yu
Larisch, Sarit
Zeng, Shelya X.
Lu, Hua
Zhou, Xiang
author_sort Hao, Qian
collection PubMed
description Apoptosis related protein in TGF-β signaling pathway (ARTS) was originally discovered in cells undergoing apoptosis in response to TGF-β, but ARTS also acts downstream of many other apoptotic stimuli. ARTS induces apoptosis by antagonizing the anti-apoptotic proteins XIAP and Bcl-2. Here we identified the pro-apoptotic Sept4/ARTS gene as a p53-responsive target gene. Ectopic p53 and a variety of p53-inducing agents increased both mRNA and protein levels of ARTS, whereas ablation of p53 reduced ARTS expression in response to multiple stress conditions. Also, γ-irradiation induced p53-dependent ARTS expression in mice. Consistently, p53 binds to the responsive DNA element on the ARTS promoter and transcriptionally activated the promoter-driven expression of a luciferase reporter gene. Interestingly, ARTS binds to and sequesters p53 at mitochondria, enhancing the interaction of the latter with Bcl-XL. Ectopic ARTS markedly augments DNA damage stress- or Nutlin-3-triggered apoptosis, while ablation of ARTS preferentially impairs p53-induced apoptosis. Altogether, these findings demonstrate that ARTS collaborates with p53 in mitochondria-engaged apoptosis.
format Online
Article
Text
id pubmed-7904775
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-79047752021-03-11 p53 induces ARTS to promote mitochondrial apoptosis Hao, Qian Chen, Jiaxiang Liao, Junming Huang, Yingdan Gan, Yu Larisch, Sarit Zeng, Shelya X. Lu, Hua Zhou, Xiang Cell Death Dis Article Apoptosis related protein in TGF-β signaling pathway (ARTS) was originally discovered in cells undergoing apoptosis in response to TGF-β, but ARTS also acts downstream of many other apoptotic stimuli. ARTS induces apoptosis by antagonizing the anti-apoptotic proteins XIAP and Bcl-2. Here we identified the pro-apoptotic Sept4/ARTS gene as a p53-responsive target gene. Ectopic p53 and a variety of p53-inducing agents increased both mRNA and protein levels of ARTS, whereas ablation of p53 reduced ARTS expression in response to multiple stress conditions. Also, γ-irradiation induced p53-dependent ARTS expression in mice. Consistently, p53 binds to the responsive DNA element on the ARTS promoter and transcriptionally activated the promoter-driven expression of a luciferase reporter gene. Interestingly, ARTS binds to and sequesters p53 at mitochondria, enhancing the interaction of the latter with Bcl-XL. Ectopic ARTS markedly augments DNA damage stress- or Nutlin-3-triggered apoptosis, while ablation of ARTS preferentially impairs p53-induced apoptosis. Altogether, these findings demonstrate that ARTS collaborates with p53 in mitochondria-engaged apoptosis. Nature Publishing Group UK 2021-02-24 /pmc/articles/PMC7904775/ /pubmed/33627621 http://dx.doi.org/10.1038/s41419-021-03463-8 Text en © The Author(s) 2021 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
Hao, Qian
Chen, Jiaxiang
Liao, Junming
Huang, Yingdan
Gan, Yu
Larisch, Sarit
Zeng, Shelya X.
Lu, Hua
Zhou, Xiang
p53 induces ARTS to promote mitochondrial apoptosis
title p53 induces ARTS to promote mitochondrial apoptosis
title_full p53 induces ARTS to promote mitochondrial apoptosis
title_fullStr p53 induces ARTS to promote mitochondrial apoptosis
title_full_unstemmed p53 induces ARTS to promote mitochondrial apoptosis
title_short p53 induces ARTS to promote mitochondrial apoptosis
title_sort p53 induces arts to promote mitochondrial apoptosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904775/
https://www.ncbi.nlm.nih.gov/pubmed/33627621
http://dx.doi.org/10.1038/s41419-021-03463-8
work_keys_str_mv AT haoqian p53inducesartstopromotemitochondrialapoptosis
AT chenjiaxiang p53inducesartstopromotemitochondrialapoptosis
AT liaojunming p53inducesartstopromotemitochondrialapoptosis
AT huangyingdan p53inducesartstopromotemitochondrialapoptosis
AT ganyu p53inducesartstopromotemitochondrialapoptosis
AT larischsarit p53inducesartstopromotemitochondrialapoptosis
AT zengshelyax p53inducesartstopromotemitochondrialapoptosis
AT luhua p53inducesartstopromotemitochondrialapoptosis
AT zhouxiang p53inducesartstopromotemitochondrialapoptosis