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Int. J. Mol. Sci. 2017, 18(12), 2581; https://doi.org/10.3390/ijms18122581

The E3 Ubiquitin Ligase RNF7 Negatively Regulates CARD14/CARMA2sh Signaling

1
Biogem Consortium, Via Camporeale, 83031 Ariano Irpino (AV), Italy
2
Genus Biotech, Università degli Studi del Sannio, Strada Statale Appia, 82010 Apollosa (BN), Italy
3
Dipartimento di Scienze e Tecnologie, Università degli Studi del Sannio, Via Port’Arsa 11, 82100 Benevento, Italy
*
Author to whom correspondence should be addressed.
Received: 25 September 2017 / Revised: 21 November 2017 / Accepted: 27 November 2017 / Published: 1 December 2017
(This article belongs to the Special Issue Ubiquitin System)
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Abstract

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. View Full-Text
Keywords: CARD14; CARMA2sh; RNF7; NF-κB; psoriasis; MALT1; ubiquitin; B-cell lymphoma/leukemia 10 (BCL10) CARD14; CARMA2sh; RNF7; NF-κB; psoriasis; MALT1; ubiquitin; B-cell lymphoma/leukemia 10 (BCL10)
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Telesio, G.; Scudiero, I.; Pizzulo, M.; Mazzone, P.; Zotti, T.; Voccola, S.; Polvere, I.; Vito, P.; Stilo, R. The E3 Ubiquitin Ligase RNF7 Negatively Regulates CARD14/CARMA2sh Signaling. Int. J. Mol. Sci. 2017, 18, 2581.

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