Cyclin-Dependent Kinase-Dependent Phosphorylation of Sox2 at Serine 39 Regulates Neurogenesis
Sox2 is known to be important for neuron formation, but the precise mechanism through which it activates a neurogenic program and how this differs from its well-established function in self-renewal of stem cells remain elusive. In this study, we identified a highly conserved cyclin-dependent kinase...
| Main Authors: | , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2017
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| Online Access: | https://hdl.handle.net/10356/84199 http://hdl.handle.net/10220/43570 |
| _version_ | 1824454500329455616 |
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| author | Lim, Shuhui Bhinge, Akshay Bragado Alonso, Sara Aksoy, Irene Aprea, Julieta Cheok, Chit Fang Calegari, Federico Stanton, Lawrence W. Kaldis, Philipp |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Lim, Shuhui Bhinge, Akshay Bragado Alonso, Sara Aksoy, Irene Aprea, Julieta Cheok, Chit Fang Calegari, Federico Stanton, Lawrence W. Kaldis, Philipp |
| author_sort | Lim, Shuhui |
| collection | NTU |
| description | Sox2 is known to be important for neuron formation, but the precise mechanism through which it activates a neurogenic program and how this differs from its well-established function in self-renewal of stem cells remain elusive. In this study, we identified a highly conserved cyclin-dependent kinase (Cdk) phosphorylation site on serine 39 (S39) in Sox2. In neural stem cells (NSCs), phosphorylation of S39 enhances the ability of Sox2 to negatively regulate neuronal differentiation, while loss of phosphorylation is necessary for chromatin retention of a truncated form of Sox2 generated during neurogenesis. We further demonstrated that nonphosphorylated cleaved Sox2 specifically induces the expression of proneural genes and promotes neurogenic commitment in vivo. Our present study sheds light on how the level of Cdk kinase activity directly regulates Sox2 to tip the balance between self-renewal and differentiation in NSCs. |
| first_indexed | 2025-02-19T03:23:18Z |
| format | Journal Article |
| id | ntu-10356/84199 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2025-02-19T03:23:18Z |
| publishDate | 2017 |
| record_format | dspace |
| spelling | ntu-10356/841992020-11-01T05:30:47Z Cyclin-Dependent Kinase-Dependent Phosphorylation of Sox2 at Serine 39 Regulates Neurogenesis Lim, Shuhui Bhinge, Akshay Bragado Alonso, Sara Aksoy, Irene Aprea, Julieta Cheok, Chit Fang Calegari, Federico Stanton, Lawrence W. Kaldis, Philipp Lee Kong Chian School of Medicine (LKCMedicine) Neural stem cells Cell cycle regulation Sox2 is known to be important for neuron formation, but the precise mechanism through which it activates a neurogenic program and how this differs from its well-established function in self-renewal of stem cells remain elusive. In this study, we identified a highly conserved cyclin-dependent kinase (Cdk) phosphorylation site on serine 39 (S39) in Sox2. In neural stem cells (NSCs), phosphorylation of S39 enhances the ability of Sox2 to negatively regulate neuronal differentiation, while loss of phosphorylation is necessary for chromatin retention of a truncated form of Sox2 generated during neurogenesis. We further demonstrated that nonphosphorylated cleaved Sox2 specifically induces the expression of proneural genes and promotes neurogenic commitment in vivo. Our present study sheds light on how the level of Cdk kinase activity directly regulates Sox2 to tip the balance between self-renewal and differentiation in NSCs. ASTAR (Agency for Sci., Tech. and Research, S’pore) Published version 2017-08-07T09:25:47Z 2019-12-06T15:40:22Z 2017-08-07T09:25:47Z 2019-12-06T15:40:22Z 2017 Journal Article Lim, S., Bhinge, A., Bragado Alonso, S., Aksoy, I., Aprea, J., Cheok, C. F., et al. (2017). Cyclin-Dependent Kinase-Dependent Phosphorylation of Sox2 at Serine 39 Regulates Neurogenesis. Molecular and Cellular Biology, 37(16), e00201-17-. 0270-7306 https://hdl.handle.net/10356/84199 http://hdl.handle.net/10220/43570 10.1128/MCB.00201-17 en Molecular and Cellular Biology © 2017 American Society for Microbiology (ASM). This paper was published in Molecular and Cellular Biology and is made available as an electronic reprint (preprint) with permission of American Society for Microbiology (ASM). The published version is available at: [http://dx.doi.org/10.1128/MCB.00201-17]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law. 24 p. application/pdf |
| spellingShingle | Neural stem cells Cell cycle regulation Lim, Shuhui Bhinge, Akshay Bragado Alonso, Sara Aksoy, Irene Aprea, Julieta Cheok, Chit Fang Calegari, Federico Stanton, Lawrence W. Kaldis, Philipp Cyclin-Dependent Kinase-Dependent Phosphorylation of Sox2 at Serine 39 Regulates Neurogenesis |
| title | Cyclin-Dependent Kinase-Dependent Phosphorylation of Sox2 at Serine 39 Regulates Neurogenesis |
| title_full | Cyclin-Dependent Kinase-Dependent Phosphorylation of Sox2 at Serine 39 Regulates Neurogenesis |
| title_fullStr | Cyclin-Dependent Kinase-Dependent Phosphorylation of Sox2 at Serine 39 Regulates Neurogenesis |
| title_full_unstemmed | Cyclin-Dependent Kinase-Dependent Phosphorylation of Sox2 at Serine 39 Regulates Neurogenesis |
| title_short | Cyclin-Dependent Kinase-Dependent Phosphorylation of Sox2 at Serine 39 Regulates Neurogenesis |
| title_sort | cyclin dependent kinase dependent phosphorylation of sox2 at serine 39 regulates neurogenesis |
| topic | Neural stem cells Cell cycle regulation |
| url | https://hdl.handle.net/10356/84199 http://hdl.handle.net/10220/43570 |
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