Non-catalytic roles for TET1 protein negatively regulating neuronal differentiation through srGAP3 in neuroblastoma cells  

作　　者：Jie Gao Yue Ma Hua-Lin Fu Qian Luo ZhenWang Yu-Huan Xiao Hao Yang Da-Xiang Cui Wei-Lin Jin 

机构地区：[1]School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China [2]institute of Nano Biomedicine and Engineering, Department of Instrument Science and Engineering, School of Electronic Information and Electronic Engineering, Shanghai Jiao Tong University, Shanghai 200240, China [3]National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, China [4]Department of Experimental Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China [5]Clinical Stem Cell Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China

出　　处：《Protein & Cell》2016年第5期351-361,共11页蛋白质与细胞（英文版）

摘　　要：The methylcytosine dioxygenases TET proteins （TET1, TET2, and TET3） play important regulatory roles in neural function. In this study, we investigated the role of TET proteins in neuronal differentiation using Neuro2a cells as a model. We observed that knockdown of TET1, TET2 or TET3 promoted neuronal differentiation of Neuro2a cells, and their overexpression inhibited VPA （valproic acid）-induced neuronal differentiation, suggesting all three TET proteins negatively regulate neu- ronal differentiation of Neuro2a cells. Interestingly, the inducing activity of TET protein is independent of its enzymatic activity. Our previous studies have demon- strated that srGAP3 can negatively regulate neuronal differentiation of Neuro2a cells. Furthermore, we revealed that TET1 could positively regulate srGAP3 expression independent of its catalytic activity, and srGAP3 is required for TET-mediated neuronal differentiation of Neuro2a cells. The results presented here may facilitate better understanding of the role of TET proteins in neuronal differentiation, and provide a possible therapy target for neuroblastoma.The methylcytosine dioxygenases TET proteins （TET1, TET2, and TET3） play important regulatory roles in neural function. In this study, we investigated the role of TET proteins in neuronal differentiation using Neuro2a cells as a model. We observed that knockdown of TET1, TET2 or TET3 promoted neuronal differentiation of Neuro2a cells, and their overexpression inhibited VPA （valproic acid）-induced neuronal differentiation, suggesting all three TET proteins negatively regulate neu- ronal differentiation of Neuro2a cells. Interestingly, the inducing activity of TET protein is independent of its enzymatic activity. Our previous studies have demon- strated that srGAP3 can negatively regulate neuronal differentiation of Neuro2a cells. Furthermore, we revealed that TET1 could positively regulate srGAP3 expression independent of its catalytic activity, and srGAP3 is required for TET-mediated neuronal differentiation of Neuro2a cells. The results presented here may facilitate better understanding of the role of TET proteins in neuronal differentiation, and provide a possible therapy target for neuroblastoma.

关 键 词：methylcytosine dioxygenase TET1 srGAP3 neuronal differentiation neuroblastoma cells 

分 类 号：Q42[生物学—神经生物学] S858.31[生物学—生理学]