LRRC25 Functions as an Inhibitor of NF-?B Signaling Pathway by Promoting p65/RelA for Autophagic Degradation.

ABSTRACT: Nuclear factor ?B (NF-?B) is a family of critical transcription factors that play a critical role in innate immune responses and inflammation, yet the molecular mechanisms responsible for its tight regulation is not fully understood. In this study, we identified LRRC25, a member of leucine-rich repeat (LRR)-containing protein family, as a negative regulator in the NF-?B signaling pathway. Ectopic expression of LRRC25 impaired NF-?B activation, whereas knockout of LRRC25 potentiated NF-?B activation and enhanced the production of inflammatory cytokines. Further study demonstrated that the LRR domain of LRRC25 interacted with the Rel Homology domain (RHD) of p65/RelA and promotes the degradation of p65/RelA. Furthermore, LRRC25 enhanced the interaction between p65/RelA and cargo receptor p62, thus facilitating the degradation of p65/RelA through autophagy pathway. Our study has not only identified LRRC25 as a novel inhibitor of NF-?B signaling pathway, but also uncovers a new mechanism of crosstalk between NF-?B signaling and autophagy pathways.

SUBMITTER: Feng Y 

PROVIDER: S-EPMC5647368 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature