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UBAC1/KPC2 Regulates TLR3 Signaling in Human Keratinocytes through Functional Interaction with the

Pellegrino Mazzone1, Michele Congestrì2, Ivan Scudiero1

  • 1Biogem Consortium, Via Camporeale, 83031 Ariano Irpino (AV), Italy.

International Journal of Molecular Sciences
|December 15, 2020
PubMed

Insights

UBA Domain Containing 1 (UBAC1) interacts with CARD14/CARMA2 in skin cells, regulating inflammatory responses. This finding sheds light on mechanisms underlying inherited inflammatory skin disorders.

Area of Science:

  • Immunology
  • Cell Biology
  • Genetics

Background:

  • CARD14/CARMA2 is a scaffold molecule implicated in inherited inflammatory skin disorders.
  • The precise mechanisms by which CARD14/CARMA2 regulates innate immunity and chronic inflammation remain unclear.

Purpose of the Study:

  • To identify novel CARD14/CARMA2 interacting proteins.
  • To elucidate the role of these interactions in regulating inflammatory signaling pathways in human keratinocytes.

Main Methods:

  • Yeast two-hybrid screening to identify CARD14/CARMA2 interactors.
  • Co-immunoprecipitation and Western blotting to confirm protein interactions and ubiquitination status.
  • Stimulation of human keratinocytes with poly (I:C) to activate Toll-like Receptor 3 and assess NF-κB activation.

Main Results:

  • Identified UBA Domain Containing 1 (UBAC1), a subunit of the KPC complex, as an interactor of CARMA2sh, a CARD14/CARMA2 isoform in keratinocytes.
  • UBAC1 forms a complex with CARMA2sh and TANK, promoting K63-linked ubiquitination of TANK.
  • UBAC1 negatively regulates CARMA2sh-mediated NF-κB activation in response to poly (I:C).

Conclusions:

  • UBAC1 acts as a negative regulator in the CARMA2sh-mediated inflammatory signaling pathway.
  • This study reveals a novel role for UBAC1 in controlling innate immune responses in keratinocytes.
  • The findings contribute to understanding the molecular basis of CARD14/CARMA2-associated inflammatory skin diseases.
Keywords:
BCL10CARD14CARMA2shNF-κBTANKUBAC1Ubiquitinpsoriasis

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