Non-catalytic roles for TET1 protein negatively regulating neuronal differentiation through srGAP3 in neuroblastoma cells
ABSTRACT 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 promot...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Oxford University Press
2016-04-01
|
| Series: | Protein & Cell |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1007/s13238-016-0267-4 |
| _version_ | 1797711555423371264 |
|---|---|
| author | Jie Gao Yue Ma Hua-Lin Fu Qian Luo Zhen Wang Yu-Huan Xiao Hao Yang Da-Xiang Cui Wei-Lin Jin |
| author_facet | Jie Gao Yue Ma Hua-Lin Fu Qian Luo Zhen Wang Yu-Huan Xiao Hao Yang Da-Xiang Cui Wei-Lin Jin |
| author_sort | Jie Gao |
| collection | DOAJ |
| description | ABSTRACT 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. |
| first_indexed | 2024-03-12T07:08:41Z |
| format | Article |
| id | doaj.art-fbe9ee5c8e59480db469a2ed892edab4 |
| institution | Directory Open Access Journal |
| issn | 1674-800X 1674-8018 |
| language | English |
| last_indexed | 2024-03-12T07:08:41Z |
| publishDate | 2016-04-01 |
| publisher | Oxford University Press |
| record_format | Article |
| series | Protein & Cell |
| spelling | doaj.art-fbe9ee5c8e59480db469a2ed892edab42023-09-02T23:18:02ZengOxford University PressProtein & Cell1674-800X1674-80182016-04-017535136110.1007/s13238-016-0267-4Non-catalytic roles for TET1 protein negatively regulating neuronal differentiation through srGAP3 in neuroblastoma cellsJie Gao0Yue Ma1Hua-Lin Fu2Qian Luo3Zhen Wang4Yu-Huan Xiao5Hao Yang6Da-Xiang Cui7Wei-Lin Jin8School of Life Sciences and Biotechnology, Shanghai Jiao Tong UniversityInstitute of Nano Biomedicine and Engineering, Department of Instrument Science and Engineering, School of Electronic Information and Electronic Engineering, Shanghai Jiao Tong UniversityInstitute of Nano Biomedicine and Engineering, Department of Instrument Science and Engineering, School of Electronic Information and Electronic Engineering, Shanghai Jiao Tong UniversitySchool of Life Sciences and Biotechnology, Shanghai Jiao Tong UniversityInstitute of Nano Biomedicine and Engineering, Department of Instrument Science and Engineering, School of Electronic Information and Electronic Engineering, Shanghai Jiao Tong UniversitySchool of Life Sciences and Biotechnology, Shanghai Jiao Tong UniversityClinical Stem Cell Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong UniversityInstitute of Nano Biomedicine and Engineering, Department of Instrument Science and Engineering, School of Electronic Information and Electronic Engineering, Shanghai Jiao Tong UniversitySchool of Life Sciences and Biotechnology, Shanghai Jiao Tong UniversityABSTRACT 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.http://link.springer.com/article/10.1007/s13238-016-0267-4methylcytosine dioxygenaseTET1srGAP3neuronal differentiationneuroblastoma cells |
| spellingShingle | Jie Gao Yue Ma Hua-Lin Fu Qian Luo Zhen Wang Yu-Huan Xiao Hao Yang Da-Xiang Cui Wei-Lin Jin Non-catalytic roles for TET1 protein negatively regulating neuronal differentiation through srGAP3 in neuroblastoma cells Protein & Cell methylcytosine dioxygenase TET1 srGAP3 neuronal differentiation neuroblastoma cells |
| title | Non-catalytic roles for TET1 protein negatively regulating neuronal differentiation through srGAP3 in neuroblastoma cells |
| title_full | Non-catalytic roles for TET1 protein negatively regulating neuronal differentiation through srGAP3 in neuroblastoma cells |
| title_fullStr | Non-catalytic roles for TET1 protein negatively regulating neuronal differentiation through srGAP3 in neuroblastoma cells |
| title_full_unstemmed | Non-catalytic roles for TET1 protein negatively regulating neuronal differentiation through srGAP3 in neuroblastoma cells |
| title_short | Non-catalytic roles for TET1 protein negatively regulating neuronal differentiation through srGAP3 in neuroblastoma cells |
| title_sort | non catalytic roles for tet1 protein negatively regulating neuronal differentiation through srgap3 in neuroblastoma cells |
| topic | methylcytosine dioxygenase TET1 srGAP3 neuronal differentiation neuroblastoma cells |
| url | http://link.springer.com/article/10.1007/s13238-016-0267-4 |
| work_keys_str_mv | AT jiegao noncatalyticrolesfortet1proteinnegativelyregulatingneuronaldifferentiationthroughsrgap3inneuroblastomacells AT yuema noncatalyticrolesfortet1proteinnegativelyregulatingneuronaldifferentiationthroughsrgap3inneuroblastomacells AT hualinfu noncatalyticrolesfortet1proteinnegativelyregulatingneuronaldifferentiationthroughsrgap3inneuroblastomacells AT qianluo noncatalyticrolesfortet1proteinnegativelyregulatingneuronaldifferentiationthroughsrgap3inneuroblastomacells AT zhenwang noncatalyticrolesfortet1proteinnegativelyregulatingneuronaldifferentiationthroughsrgap3inneuroblastomacells AT yuhuanxiao noncatalyticrolesfortet1proteinnegativelyregulatingneuronaldifferentiationthroughsrgap3inneuroblastomacells AT haoyang noncatalyticrolesfortet1proteinnegativelyregulatingneuronaldifferentiationthroughsrgap3inneuroblastomacells AT daxiangcui noncatalyticrolesfortet1proteinnegativelyregulatingneuronaldifferentiationthroughsrgap3inneuroblastomacells AT weilinjin noncatalyticrolesfortet1proteinnegativelyregulatingneuronaldifferentiationthroughsrgap3inneuroblastomacells |