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Updated: Oct 8, 2025

NF-κB-dependent Luciferase Activation and Quantification of Gene Expression in Salmonella Infected Tissue Culture Cells
Published on: January 12, 2020
Immune regulator LGP2 targets Ubc13/UBE2N to mediate widespread interference with K63 polyubiquitination and NF-κB
Jessica J Lenoir1, Jean-Patrick Parisien1, Curt M Horvath1
1Department of Molecular Biosciences, Northwestern University, Evanston, IL, USA.
Abstract:
Lysine 63-linked polyubiquitin (K63-Ub) chains activate a range of cellular immune and inflammatory signaling pathways, including the mammalian antiviral response. Interferon and antiviral genes are triggered by TRAF family ubiquitin ligases that form K63-Ub chains. LGP2 is a feedback inhibitor of TRAF-mediated K63-Ub that can interfere with diverse immune signaling pathways. Our results demonstrate that LGP2 inhibits K63-Ub by association with and sequestration of the K63-Ub-conjugating enzyme, Ubc13/UBE2N. The LGP2 helicase subdomain, Hel2i, mediates protein interaction that engages and inhibits Ubc13/UBE2N, affecting control over a range of K63-Ub ligase proteins, including TRAF6, TRIM25, and RNF125, all of which are inactivated by LGP2. These findings establish a unifying mechanism for LGP2-mediated negative regulation that can modulate a variety of K63-Ub signaling pathways.
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