UBAC1/KPC2 Regulates TLR3 Signaling in Human Keratinocytes through Functional Interaction with the CARD14/CARMA2sh-TANK Complex.

Pellegrino Mazzone, Michele Congestrì, Ivan Scudiero, Immacolata Polvere, Serena Voccola, Lucrezia Zerillo, Gianluca Telesio, Pasquale Vito, Romania Stilo, Tiziana Zotti

International journal of molecular sciences 2020 Dec 09

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CARD14/CARMA2 is a scaffold molecule whose genetic alterations are linked to human inherited inflammatory skin disorders. However, the mechanisms through which CARD14/CARMA2 controls innate immune response and chronic inflammation are not well understood. By means of a yeast two-hybrid screening, we identified the UBA Domain Containing 1 (UBAC1), the non-catalytic subunit of the E3 ubiquitin-protein ligase KPC complex, as an interactor of CARMA2sh, the CARD14/CARMA2 isoform mainly expressed in human keratinocytes. UBAC1 participates in the CARMA2sh/TANK complex and promotes K63-linked ubiquitination of TANK. In human keratinocytes, UBAC1 negatively regulates the NF-κF-activating capacity of CARMA2sh following exposure to poly (I:C), an agonist of Toll-like Receptor 3. Overall, our data indicate that UBAC1 participates in the inflammatory signal transduction pathways involving CARMA2sh.

Citation

Pellegrino Mazzone, Michele Congestrì, Ivan Scudiero, Immacolata Polvere, Serena Voccola, Lucrezia Zerillo, Gianluca Telesio, Pasquale Vito, Romania Stilo, Tiziana Zotti. UBAC1/KPC2 Regulates TLR3 Signaling in Human Keratinocytes through Functional Interaction with the CARD14/CARMA2sh-TANK Complex. International journal of molecular sciences. 2020 Dec 09;21(24)