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Immune regulator LGP2 targets Ubc13/UBE2N to mediate widespread interference with K63 polyubiquitination and NF-κB activation.

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.

SUBMITTER: Lenoir JJ 

PROVIDER: S-EPMC8787715 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Publications

The Role of Monk Parakeets as Nest-Site Facilitators in Their Native and Invaded Areas.

Hernández-Brito Dailos D   Carrete Martina M   Blanco Guillermo G   Romero-Vidal Pedro P   Senar Juan Carlos JC   Mori Emiliano E   White Thomas H TH   Luna Álvaro Á   Tella José L JL  

Biology 20210719 7

While most of the knowledge on invasive species focuses on their impacts, little is known about their potential positive effects on other species. Invasive ecosystem engineers can disrupt recipient environments; however, they may also facilitate access to novel resources for native species. The monk parakeet (<i>Myiopsitta monachus</i>) is a worldwide invader and the only parrot that builds its own communal nests, which can be used by other species. However, the ecological effects of these inter  ...[more]

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