title: LRRC14 attenuates Toll-like receptor-mediated NF-κB signaling through disruption of IKK complex.
abstract: Activation of NF-κB signaling plays pivotal roles in innate immune responses against pathogens. It requires strict control to avert inflammatory diseases. However, the mechanisms underlying this tight regulation are not completely understood. Here, we identified LRRC14, a novel member of LRR (leucine-rich repeat) protein family, as a negative regulator in TLR signaling. Expression of LRRC14 resulted in decreased activation of NF-κB, whereas knockdown of LRRC14 enhanced NF-κB activation as well as the production of inflammatory cytokines. Mechanistically, LRRC14 bound to HLH domain of IKKβ to block its interaction with NEMO and thereby inhibiting the phosphorylation of IKKβ and NF-κB activation. In addition, our data showed that TLR signaling led to lower expression of LRRC14. Together, LRRC14 may function as a checkpoint to prevent overzealous inflammation.
authors.affiliation: Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Chenglei
authors.initials: C
authors.lastname: Wu
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yexin
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jiayu
authors.initials: J
authors.lastname: Ou
authors.affiliation: Hangzhou Normal University, Hang Zhou, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China. Electronic address: cuij5@mail.sysu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Cui
mesh_terms: D000818:Animals; D002460:Cell Line; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D000090263:Leucine-Rich Repeat Proteins; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: C491731:IKBKG protein, human; D000090263:Leucine-Rich Repeat Proteins; D016328:NF-kappa B; D011506:Proteins; D012333:RNA, Messenger; D051193:Toll-Like Receptors; D051550:I-kappa B Kinase
keywords: IKKβ; Leucine-rich repeat; NF-κB; Phosphorylation; Toll-like receptor