2. Academic Validation
  3. LRRC25 Functions as an Inhibitor of NF-κB Signaling Pathway by Promoting p65/RelA for Autophagic Degradation

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

  • Sci Rep. 2017 Oct 18;7(1):13448. doi: 10.1038/s41598-017-12573-3.
Yanchun Feng 1 2,  Tianhao Duan 1 2,  Yang Du 1 2,  Shouheng Jin 2,  Mingjun Wang 3,  Jun Cui 4,  Rong-Fu Wang 5 6
Affiliations

Affiliations

  • 1 Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
  • 2 Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China.
  • 3 Shenzhen Institute for Innovation and Translational Medicine, Shenzhen, 518120, China.
  • 4 Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China. cuij5@mail.sysu.edu.cn.
  • 5 Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, Texas, 77030, USA. rwang3@houstonmethodist.org.
  • 6 Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY, 10065, USA. rwang3@houstonmethodist.org.
PMID: 29044191 DOI: 10.1038/s41598-017-12573-3
Abstract

Nuclear factor κB (NF-κB) 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-κB signaling pathway. Ectopic expression of LRRC25 impaired NF-κB activation, whereas knockout of LRRC25 potentiated NF-κB 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-κB signaling pathway, but also uncovers a new mechanism of crosstalk between NF-κB signaling and Autophagy pathways.

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