Immune regulator LGP2 targets Ubc13/UBE2N to mediate widespread interference with K63 polyubiquitination and NF-?B activation.
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.
Mesh Terms:
Cytokines, Gene Expression Regulation, Humans, Interferon Regulatory Factor-3, Intracellular Signaling Peptides and Proteins, Lysine, NF-kappa B, RNA Helicases, Signal Transduction, TNF Receptor-Associated Factor 6, Ubiquitin, Ubiquitin-Conjugating Enzymes, Ubiquitination
Cytokines, Gene Expression Regulation, Humans, Interferon Regulatory Factor-3, Intracellular Signaling Peptides and Proteins, Lysine, NF-kappa B, RNA Helicases, Signal Transduction, TNF Receptor-Associated Factor 6, Ubiquitin, Ubiquitin-Conjugating Enzymes, Ubiquitination
Cell Rep
Date: Dec. 28, 2020
PubMed ID: 34965427
View in: Pubmed Google Scholar
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