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The Hh pathway promotes cell apoptosis through Ci-Rdx-Diap1 axis

Apoptosis is a strictly coordinated process to eliminate superfluous or damaged cells, and its deregulation leads to birth defects and various human diseases. The regulatory mechanism underlying apoptosis still remains incompletely understood. To identify novel components in apoptosis, we carry out...

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Detalles Bibliográficos
Autores principales: Liu, Bin, Ding, Yan, Sun, Bing, Liu, Qingxin, Zhou, Zizhang, Zhan, Meixiao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463586/
https://www.ncbi.nlm.nih.gov/pubmed/34561426
http://dx.doi.org/10.1038/s41420-021-00653-3
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author Liu, Bin
Ding, Yan
Sun, Bing
Liu, Qingxin
Zhou, Zizhang
Zhan, Meixiao
author_facet Liu, Bin
Ding, Yan
Sun, Bing
Liu, Qingxin
Zhou, Zizhang
Zhan, Meixiao
author_sort Liu, Bin
collection PubMed
description Apoptosis is a strictly coordinated process to eliminate superfluous or damaged cells, and its deregulation leads to birth defects and various human diseases. The regulatory mechanism underlying apoptosis still remains incompletely understood. To identify novel components in apoptosis, we carry out a modifier screen and find that the Hh pathway aggravates Hid-induced apoptosis. In addition, we reveal that the Hh pathway triggers apoptosis through its transcriptional target gene rdx, which encodes an E3 ubiquitin ligase. Rdx physically binds Diap1 to promote its K63-linked polyubiquitination, culminating in attenuating Diap1−Dronc interaction without affecting Diap1 stability. Taken together, our findings unexpectedly uncover the oncogenic Hh pathway is able to promote apoptosis through Ci-Rdx-Diap1 module, raising a concern to choose Hh pathway inhibitors as anti-tumor drugs.
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spelling pubmed-84635862021-10-08 The Hh pathway promotes cell apoptosis through Ci-Rdx-Diap1 axis Liu, Bin Ding, Yan Sun, Bing Liu, Qingxin Zhou, Zizhang Zhan, Meixiao Cell Death Discov Article Apoptosis is a strictly coordinated process to eliminate superfluous or damaged cells, and its deregulation leads to birth defects and various human diseases. The regulatory mechanism underlying apoptosis still remains incompletely understood. To identify novel components in apoptosis, we carry out a modifier screen and find that the Hh pathway aggravates Hid-induced apoptosis. In addition, we reveal that the Hh pathway triggers apoptosis through its transcriptional target gene rdx, which encodes an E3 ubiquitin ligase. Rdx physically binds Diap1 to promote its K63-linked polyubiquitination, culminating in attenuating Diap1−Dronc interaction without affecting Diap1 stability. Taken together, our findings unexpectedly uncover the oncogenic Hh pathway is able to promote apoptosis through Ci-Rdx-Diap1 module, raising a concern to choose Hh pathway inhibitors as anti-tumor drugs. Nature Publishing Group UK 2021-09-24 /pmc/articles/PMC8463586/ /pubmed/34561426 http://dx.doi.org/10.1038/s41420-021-00653-3 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Liu, Bin
Ding, Yan
Sun, Bing
Liu, Qingxin
Zhou, Zizhang
Zhan, Meixiao
The Hh pathway promotes cell apoptosis through Ci-Rdx-Diap1 axis
title The Hh pathway promotes cell apoptosis through Ci-Rdx-Diap1 axis
title_full The Hh pathway promotes cell apoptosis through Ci-Rdx-Diap1 axis
title_fullStr The Hh pathway promotes cell apoptosis through Ci-Rdx-Diap1 axis
title_full_unstemmed The Hh pathway promotes cell apoptosis through Ci-Rdx-Diap1 axis
title_short The Hh pathway promotes cell apoptosis through Ci-Rdx-Diap1 axis
title_sort hh pathway promotes cell apoptosis through ci-rdx-diap1 axis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463586/
https://www.ncbi.nlm.nih.gov/pubmed/34561426
http://dx.doi.org/10.1038/s41420-021-00653-3
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