Negative regulation of NEMO signaling by the ubiquitin E3 ligase MARCH2.

ABSTRACT: NF-κB essential modulator (NEMO) is a key regulatory protein that functions during NF-κB- and interferon-mediated signaling in response to extracellular stimuli and pathogen infections. Tight regulation of NEMO is essential for host innate immune responses and for maintenance of homeostasis. Here, we report that the E3 ligase MARCH2 is a novel negative regulator of NEMO-mediated signaling upon bacterial or viral infection. MARCH2 interacted directly with NEMO during the late phase of infection and catalyzed K-48-linked ubiquitination of Lys326 on NEMO, which resulted in its degradation. Deletion of MARCH2 resulted in marked resistance to bacterial/viral infection, along with increased innate immune responses both in vitro and in vivo. In addition, MARCH2^-/- mice were more suscep

SUBMITTER: Chathuranga K 

PROVIDER: S-EPMC7604578 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature