UBAC1/KPC2 Regulates TLR3 Signaling in Human Keratinocytes through Functional Interaction with the CARD14/CARMA2sh-TANK Complex.
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-?F-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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, CARD Signaling Adaptor Proteins, Guanylate Cyclase, HEK293 Cells, HaCaT Cells, Humans, Membrane Proteins, NF-kappa B, Protein Binding, Signal Transduction, Toll-Like Receptor 3, Ubiquitin-Protein Ligases, Ubiquitination
Adaptor Proteins, Signal Transducing, CARD Signaling Adaptor Proteins, Guanylate Cyclase, HEK293 Cells, HaCaT Cells, Humans, Membrane Proteins, NF-kappa B, Protein Binding, Signal Transduction, Toll-Like Receptor 3, Ubiquitin-Protein Ligases, Ubiquitination
Int J Mol Sci
Date: Dec. 09, 2020
PubMed ID: 33316896
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