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

International Journal of Molecular Sciences

Gianluca Telesio¹  Ivan Scudiero¹  Pellegrino Mazzone¹  Tiziana Zotti²  Michele Congestrì²  Romania Stilo²  Immacolata Polvere²  Pasquale Vito²  Serena Voccola³  Lucrezia Zerillo³ 

[1] Biogem Consortium, Via Camporeale, 83031 Ariano Irpino (AV), Italy;Dipartimento di Scienze e Tecnologie, Università degli Studi del Sannio, Via Port’Arsa 11, 82100 Benevento, Italy;Genus Biotech, Università degli Studi del Sannio, Via Appia snc, 82030 Apollosa (BN), Italy;

关键词: CARD14;    CARMA2sh;    UBAC1;    NF-κB;    psoriasis;    TANK;   

DOI  :  10.3390/ijms21249365

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown