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The E3 Ubiquitin-Protein Ligase RNF4 Promotes TNF-α-Induced Cell Death Triggered by RIPK1
Receptor-interacting protein kinase 1 (RIPK1) is a key component of the tumor necrosis factor (TNF) receptor signaling complex that regulates both pro- and anti-apoptotic signaling. The reciprocal functions of RIPK1 in TNF signaling are determined by the state of the posttranslational modifications...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199362/ https://www.ncbi.nlm.nih.gov/pubmed/34071450 http://dx.doi.org/10.3390/ijms22115796 |
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author | Shimada, Tatsuya Kudoh, Yuki Noguchi, Takuya Kagi, Tomohiro Suzuki, Midori Tsuchida, Mei Komatsu, Hiromu Takahashi, Miki Hirata, Yusuke Matsuzawa, Atsushi |
author_facet | Shimada, Tatsuya Kudoh, Yuki Noguchi, Takuya Kagi, Tomohiro Suzuki, Midori Tsuchida, Mei Komatsu, Hiromu Takahashi, Miki Hirata, Yusuke Matsuzawa, Atsushi |
author_sort | Shimada, Tatsuya |
collection | PubMed |
description | Receptor-interacting protein kinase 1 (RIPK1) is a key component of the tumor necrosis factor (TNF) receptor signaling complex that regulates both pro- and anti-apoptotic signaling. The reciprocal functions of RIPK1 in TNF signaling are determined by the state of the posttranslational modifications (PTMs) of RIPK1. However, the underlying mechanisms associated with the PTMs of RIPK1 are unclear. In this study, we found that RING finger protein 4 (RNF4), a RING finger E3 ubiquitin ligase, is required for the RIPK1 autophosphorylation and subsequent cell death. It has been reported that RNF4 negatively regulates TNF-α-induced activation of the nuclear factor-κB (NF-κB) through downregulation of transforming growth factor β-activated kinase 1 (TAK1) activity, indicating the possibility that RNF4-mediated TAK1 suppression results in enhanced sensitivity to cell death. However, interestingly, RNF4 was needed to induce RIPK1-mediated cell death even in the absence of TAK1, suggesting that RNF4 can promote RIPK1-mediated cell death without suppressing the TAK1 activity. Thus, these observations reveal the existence of a novel mechanism whereby RNF4 promotes the autophosphorylation of RIPK1, which provides a novel insight into the molecular basis for the PTMs of RIPK1. |
format | Online Article Text |
id | pubmed-8199362 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-81993622021-06-14 The E3 Ubiquitin-Protein Ligase RNF4 Promotes TNF-α-Induced Cell Death Triggered by RIPK1 Shimada, Tatsuya Kudoh, Yuki Noguchi, Takuya Kagi, Tomohiro Suzuki, Midori Tsuchida, Mei Komatsu, Hiromu Takahashi, Miki Hirata, Yusuke Matsuzawa, Atsushi Int J Mol Sci Article Receptor-interacting protein kinase 1 (RIPK1) is a key component of the tumor necrosis factor (TNF) receptor signaling complex that regulates both pro- and anti-apoptotic signaling. The reciprocal functions of RIPK1 in TNF signaling are determined by the state of the posttranslational modifications (PTMs) of RIPK1. However, the underlying mechanisms associated with the PTMs of RIPK1 are unclear. In this study, we found that RING finger protein 4 (RNF4), a RING finger E3 ubiquitin ligase, is required for the RIPK1 autophosphorylation and subsequent cell death. It has been reported that RNF4 negatively regulates TNF-α-induced activation of the nuclear factor-κB (NF-κB) through downregulation of transforming growth factor β-activated kinase 1 (TAK1) activity, indicating the possibility that RNF4-mediated TAK1 suppression results in enhanced sensitivity to cell death. However, interestingly, RNF4 was needed to induce RIPK1-mediated cell death even in the absence of TAK1, suggesting that RNF4 can promote RIPK1-mediated cell death without suppressing the TAK1 activity. Thus, these observations reveal the existence of a novel mechanism whereby RNF4 promotes the autophosphorylation of RIPK1, which provides a novel insight into the molecular basis for the PTMs of RIPK1. MDPI 2021-05-28 /pmc/articles/PMC8199362/ /pubmed/34071450 http://dx.doi.org/10.3390/ijms22115796 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Shimada, Tatsuya Kudoh, Yuki Noguchi, Takuya Kagi, Tomohiro Suzuki, Midori Tsuchida, Mei Komatsu, Hiromu Takahashi, Miki Hirata, Yusuke Matsuzawa, Atsushi The E3 Ubiquitin-Protein Ligase RNF4 Promotes TNF-α-Induced Cell Death Triggered by RIPK1 |
title | The E3 Ubiquitin-Protein Ligase RNF4 Promotes TNF-α-Induced Cell Death Triggered by RIPK1 |
title_full | The E3 Ubiquitin-Protein Ligase RNF4 Promotes TNF-α-Induced Cell Death Triggered by RIPK1 |
title_fullStr | The E3 Ubiquitin-Protein Ligase RNF4 Promotes TNF-α-Induced Cell Death Triggered by RIPK1 |
title_full_unstemmed | The E3 Ubiquitin-Protein Ligase RNF4 Promotes TNF-α-Induced Cell Death Triggered by RIPK1 |
title_short | The E3 Ubiquitin-Protein Ligase RNF4 Promotes TNF-α-Induced Cell Death Triggered by RIPK1 |
title_sort | e3 ubiquitin-protein ligase rnf4 promotes tnf-α-induced cell death triggered by ripk1 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199362/ https://www.ncbi.nlm.nih.gov/pubmed/34071450 http://dx.doi.org/10.3390/ijms22115796 |
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