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The E3 Ubiquitin Ligase RNF7 Negatively Regulates CARD14/CARMA2sh Signaling

The three CARD-containing MAGUK (CARMA) proteins function as scaffolding molecules that regulate activation of the pro-inflammatory transcription factor NF-κB. Recently, mutations in CARMA2 have been linked to psoriasis susceptibility due to their acquired altered capacity to activate NF-κB. By mean...

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Autores principales: Telesio, Gianluca, Scudiero, Ivan, Pizzulo, Maddalena, Mazzone, Pellegrino, Zotti, Tiziana, Voccola, Serena, Polvere, Immacolata, Vito, Pasquale, Stilo, Romania
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5751184/
https://www.ncbi.nlm.nih.gov/pubmed/29194363
http://dx.doi.org/10.3390/ijms18122581
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author Telesio, Gianluca
Scudiero, Ivan
Pizzulo, Maddalena
Mazzone, Pellegrino
Zotti, Tiziana
Voccola, Serena
Polvere, Immacolata
Vito, Pasquale
Stilo, Romania
author_facet Telesio, Gianluca
Scudiero, Ivan
Pizzulo, Maddalena
Mazzone, Pellegrino
Zotti, Tiziana
Voccola, Serena
Polvere, Immacolata
Vito, Pasquale
Stilo, Romania
author_sort Telesio, Gianluca
collection PubMed
description The three CARD-containing MAGUK (CARMA) proteins function as scaffolding molecules that regulate activation of the pro-inflammatory transcription factor NF-κB. Recently, mutations in CARMA2 have been linked to psoriasis susceptibility due to their acquired altered capacity to activate NF-κB. By means of two-hybrid screening with yeast, we identified RING finger protein 7 (RNF7) as an interactor of CARMA2. We present evidence that RNF7 functions as a negative regulator of the NF-κB-activating capacity of CARMA2. Mechanistically, RNF7 influences CARMA2 signaling by regulating the ubiquitination state of MALT1 and the NF-κB-regulatory molecule NEMO. Interestingly, CARMA2short (CARMA2sh) mutants associated with psoriasis susceptibility escape the negative control exerted by RNF7. In conclusion, our findings identify a new mechanism through which the ability of CARMA2 to activate NF-κB is regulated, which could have significant implications for our understanding of why mutations of this protein trigger human psoriasis.
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spelling pubmed-57511842018-01-08 The E3 Ubiquitin Ligase RNF7 Negatively Regulates CARD14/CARMA2sh Signaling Telesio, Gianluca Scudiero, Ivan Pizzulo, Maddalena Mazzone, Pellegrino Zotti, Tiziana Voccola, Serena Polvere, Immacolata Vito, Pasquale Stilo, Romania Int J Mol Sci Article The three CARD-containing MAGUK (CARMA) proteins function as scaffolding molecules that regulate activation of the pro-inflammatory transcription factor NF-κB. Recently, mutations in CARMA2 have been linked to psoriasis susceptibility due to their acquired altered capacity to activate NF-κB. By means of two-hybrid screening with yeast, we identified RING finger protein 7 (RNF7) as an interactor of CARMA2. We present evidence that RNF7 functions as a negative regulator of the NF-κB-activating capacity of CARMA2. Mechanistically, RNF7 influences CARMA2 signaling by regulating the ubiquitination state of MALT1 and the NF-κB-regulatory molecule NEMO. Interestingly, CARMA2short (CARMA2sh) mutants associated with psoriasis susceptibility escape the negative control exerted by RNF7. In conclusion, our findings identify a new mechanism through which the ability of CARMA2 to activate NF-κB is regulated, which could have significant implications for our understanding of why mutations of this protein trigger human psoriasis. MDPI 2017-12-01 /pmc/articles/PMC5751184/ /pubmed/29194363 http://dx.doi.org/10.3390/ijms18122581 Text en © 2017 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Telesio, Gianluca
Scudiero, Ivan
Pizzulo, Maddalena
Mazzone, Pellegrino
Zotti, Tiziana
Voccola, Serena
Polvere, Immacolata
Vito, Pasquale
Stilo, Romania
The E3 Ubiquitin Ligase RNF7 Negatively Regulates CARD14/CARMA2sh Signaling
title The E3 Ubiquitin Ligase RNF7 Negatively Regulates CARD14/CARMA2sh Signaling
title_full The E3 Ubiquitin Ligase RNF7 Negatively Regulates CARD14/CARMA2sh Signaling
title_fullStr The E3 Ubiquitin Ligase RNF7 Negatively Regulates CARD14/CARMA2sh Signaling
title_full_unstemmed The E3 Ubiquitin Ligase RNF7 Negatively Regulates CARD14/CARMA2sh Signaling
title_short The E3 Ubiquitin Ligase RNF7 Negatively Regulates CARD14/CARMA2sh Signaling
title_sort e3 ubiquitin ligase rnf7 negatively regulates card14/carma2sh signaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5751184/
https://www.ncbi.nlm.nih.gov/pubmed/29194363
http://dx.doi.org/10.3390/ijms18122581
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