Non-catalytic roles for TET1 protein negatively regulating neuronal differentiation through srGAP3 in neuroblastoma cells.
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 neuronal differentiation of Neuro2a cells. Interestingly, the inducing activity of TET protein is independent of its enzymatic activity. Our previous studies have demonstrated 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.
School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China.|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.
Jie
J
Gao
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.
Yue
Y
Ma
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.|National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China.
Hua-Lin
HL
Fu
School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China.
Qian
Q
Luo
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.|Department of Experimental Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, China.
Zhen
Z
Wang
School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China.|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.
Yu-Huan
YH
Xiao
Clinical Stem Cell Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
Hao
H
Yang
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.|National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China.
Da-Xiang
DX
Cui
School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China. weilinjin@sjtu.edu.cn.|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. weilinjin@sjtu.edu.cn.|National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China. weilinjin@sjtu.edu.cn.
Wei-Lin
WL
Jin
D000818:Animals; D020134:Catalytic Domain; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008856:Microscopy, Fluorescence; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D014635:Valproic Acid / Q000494:pharmacology
D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D020690:GTPase-Activating Proteins; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C516731:Srgap3 protein, mouse; C540839:TET1 protein, mouse; D014635:Valproic Acid
TET1; methylcytosine dioxygenase; neuroblastoma cells; neuronal differentiation; srGAP3