IJMS, Vol. 18, Pages 2581: The E3 Ubiquitin Ligase RNF7 Negatively Regulates CARD14/CARMA2sh Signaling

IJMS, Vol. 18, Pages 2581: The E3 Ubiquitin Ligase RNF7 Negatively Regulates CARD14/CARMA2sh Signaling

International Journal of Molecular Sciences doi: 10.3390/ijms18122581

Authors: Gianluca Telesio Ivan Scudiero Maddalena Pizzulo Pellegrino Mazzone Tiziana Zotti Serena Voccola Immacolata Polvere Pasquale Vito Romania Stilo

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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