Article Neuroglobin Regulates Wnt/beta-Catenin and NF kappa B Signaling Pathway through Dvl1

作者：Xun, Yu; Li, Zhen; Tang, Yingxin; Yang, Manjun; Long, Shengwen; Shu, Pan; Li, Jiabing; Xiao, Ye; Tang, Fen; Wei, Chenxi; Liu, Ning^*; Xiang, Shuanglin^*

来源：International Journal of Molecular Sciences, 2018, 19(7): 2133.

DOI：10.3390/ijms19072133

• Ngb
• Dvl1
• NF kappa B
• Wnt/beta-Catenin
• SK-N-SH

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/beta-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/beta-Catenin and NF kappa B 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 beta-Catenin mediated by Dishevelled-1 in SK-N-SH cells. In addition, we also documented that Neuroglobin enhances TNF-alpha-induced NF kappa B 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-alpha-induced decrease in cell viability. Taken together, these findings demonstrated that Neuroglobin functions as an important modulator of the Wnt/beta-Catenin and NF kappa B signaling pathway through regulating Dishevelled-1.

• 出版日期2018-7
• 单位湖南师范大学