RIPK1 and TRADD Regulate TNF-Induced Signaling and Ripoptosome Formation

TNF is a proinflammatory cytokine that is critical for the coordination of tissue homeostasis. RIPK1 and TRADD are the main participants in the transduction of TNF signaling. However, data on the cell fate-controlling functions of both molecules are quite controversial. Here, we address the function...

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Autores principales:	Maria Feoktistova, Roman Makarov, Amir S. Yazdi, Diana Panayotova-Dimitrova
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	TNF signaling NF-κB apoptosis necroptosis ripoptosome NIK Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/d1ee5071d4d7482699dbbb83d6a31fe9
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spelling	oai:doaj.org-article:d1ee5071d4d7482699dbbb83d6a31fe92021-11-25T17:56:54ZRIPK1 and TRADD Regulate TNF-Induced Signaling and Ripoptosome Formation10.3390/ijms2222124591422-00671661-6596https://doaj.org/article/d1ee5071d4d7482699dbbb83d6a31fe92021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12459https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067TNF is a proinflammatory cytokine that is critical for the coordination of tissue homeostasis. RIPK1 and TRADD are the main participants in the transduction of TNF signaling. However, data on the cell fate-controlling functions of both molecules are quite controversial. Here, we address the functions of RIPK1 and TRADD in TNF signaling by generating RIPK1- or TRADD-deficient human cell lines. We demonstrate that RIPK1 is relevant for TNF-induced apoptosis and necroptosis in conditions with depleted IAPs. In addition, TRADD is dispensable for necroptosis but required for apoptosis. We reveal a new possible function of TRADD as a negative regulator of NIK stabilization and subsequent ripoptosome formation. Furthermore, we show that RIPK1 and TRADD do not appear to be essential for the activation of MAPK signaling. Moreover, partially repressing NF-κB activation in both RIPK1 and TRADD KO cells does not result in sensitization to TNF alone due to the absence of NIK stabilization. Importantly, we demonstrate that RIPK1 is essential for preventing TRADD from undergoing TNF-induced ubiquitination and degradation. Taken together, our findings provide further insights into the specific functions of RIPK1 and TRADD in the regulation of TNF-dependent signaling, which controls the balance between cell death and survival.Maria FeoktistovaRoman MakarovAmir S. YazdiDiana Panayotova-DimitrovaMDPI AGarticleTNF signalingNF-κBapoptosisnecroptosisripoptosomeNIKBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12459, p 12459 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	TNF signaling NF-κB apoptosis necroptosis ripoptosome NIK Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	TNF signaling NF-κB apoptosis necroptosis ripoptosome NIK Biology (General) QH301-705.5 Chemistry QD1-999 Maria Feoktistova Roman Makarov Amir S. Yazdi Diana Panayotova-Dimitrova RIPK1 and TRADD Regulate TNF-Induced Signaling and Ripoptosome Formation
description	TNF is a proinflammatory cytokine that is critical for the coordination of tissue homeostasis. RIPK1 and TRADD are the main participants in the transduction of TNF signaling. However, data on the cell fate-controlling functions of both molecules are quite controversial. Here, we address the functions of RIPK1 and TRADD in TNF signaling by generating RIPK1- or TRADD-deficient human cell lines. We demonstrate that RIPK1 is relevant for TNF-induced apoptosis and necroptosis in conditions with depleted IAPs. In addition, TRADD is dispensable for necroptosis but required for apoptosis. We reveal a new possible function of TRADD as a negative regulator of NIK stabilization and subsequent ripoptosome formation. Furthermore, we show that RIPK1 and TRADD do not appear to be essential for the activation of MAPK signaling. Moreover, partially repressing NF-κB activation in both RIPK1 and TRADD KO cells does not result in sensitization to TNF alone due to the absence of NIK stabilization. Importantly, we demonstrate that RIPK1 is essential for preventing TRADD from undergoing TNF-induced ubiquitination and degradation. Taken together, our findings provide further insights into the specific functions of RIPK1 and TRADD in the regulation of TNF-dependent signaling, which controls the balance between cell death and survival.
format	article
author	Maria Feoktistova Roman Makarov Amir S. Yazdi Diana Panayotova-Dimitrova
author_facet	Maria Feoktistova Roman Makarov Amir S. Yazdi Diana Panayotova-Dimitrova
author_sort	Maria Feoktistova
title	RIPK1 and TRADD Regulate TNF-Induced Signaling and Ripoptosome Formation
title_short	RIPK1 and TRADD Regulate TNF-Induced Signaling and Ripoptosome Formation
title_full	RIPK1 and TRADD Regulate TNF-Induced Signaling and Ripoptosome Formation
title_fullStr	RIPK1 and TRADD Regulate TNF-Induced Signaling and Ripoptosome Formation
title_full_unstemmed	RIPK1 and TRADD Regulate TNF-Induced Signaling and Ripoptosome Formation
title_sort	ripk1 and tradd regulate tnf-induced signaling and ripoptosome formation
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/d1ee5071d4d7482699dbbb83d6a31fe9
work_keys_str_mv	AT mariafeoktistova ripk1andtraddregulatetnfinducedsignalingandripoptosomeformation AT romanmakarov ripk1andtraddregulatetnfinducedsignalingandripoptosomeformation AT amirsyazdi ripk1andtraddregulatetnfinducedsignalingandripoptosomeformation AT dianapanayotovadimitrova ripk1andtraddregulatetnfinducedsignalingandripoptosomeformation
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RIPK1 and TRADD Regulate TNF-Induced Signaling and Ripoptosome Formation

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