Neuroglobin Regulates Wnt/β-Catenin and NFκB Signaling Pathway through Dvl1

• Main Authors: Yu Xun, Zhen Li, Yingxin Tang, Manjun Yang, Shengwen Long, Pan Shu, Jiabing Li, Ye Xiao, Fen Tang, Chenxi Wei, Ning Liu, Shuanglin Xiang
• Format: Article
• Language: English
• Published: MDPI AG 2018-07-01
• Series: International Journal of Molecular Sciences
• Subjects: Ngb; Dvl1; NFκB; Wnt/β-Catenin; SK-N-SH
• Online Access: http://www.mdpi.com/1422-0067/19/7/2133

Neuroglobin is an endogenous neuroprotective protein, but the underlying neuroprotective mechanisms remain to be elucidated. Our previous yeast two-hybrid screening study identified that Dishevelled-1, a key hub protein of Wnt/β-Catenin signaling, is an interaction partner of Neuroglobin. In this study, we further examined the role of Neuroglobin in regulating Dishevelled-1 and the downstream Wnt/β-Catenin and NFκB signaling pathway. We found that Neuroglobin directly interacts with Dishevelled-1 by co-immunoprecipitation, and the two proteins are co-localized in both cytoplasma and nucleus of SK-N-SH cells. Moreover, the ectopic expression of Neuroglobin promotes the degradation of exogenous and endogenous Dishevelled-1 through the proteasomal degradation pathway. Furthermore, our results showed that Neuroglobin significantly inhibits the luciferase activity of Topflash reporter and the expression of β-Catenin mediated by Dishevelled-1 in SK-N-SH cells. In addition, we also documented that Neuroglobin enhances TNF-α-induced NFκB activation via down-regulating Dishevelled-1. Finally, 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) assays showed that Neuroglobin is an important neuroprotectant that protects SK-N-SH cells from TNF-α-induced decrease in cell viability. Taken together, these findings demonstrated that Neuroglobin functions as an important modulator of the Wnt/β-Catenin and NFκB signaling pathway through regulating Dishevelled-1.