The E3 Ubiquitin Ligase RNF7 Negatively Regulates CARD14/CARMA2sh Signaling
AbstractThe 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
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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.
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. International Journal of Molecular Sciences. 2017; 18(12):2581.Chicago/Turabian Style
Telesio, Gianluca; Scudiero, Ivan; Pizzulo, Maddalena; Mazzone, Pellegrino; Zotti, Tiziana; Voccola, Serena; Polvere, Immacolata; Vito, Pasquale; Stilo, Romania. 2017. "The E3 Ubiquitin Ligase RNF7 Negatively Regulates CARD14/CARMA2sh Signaling." Int. J. Mol. Sci. 18, no. 12: 2581.
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