Cyclin-Dependent Kinase-Dependent Phosphorylation of Sox2 at Serine 39 Regulates Neurogenesis
| Autor: | Chit Fang Cheok, Irene Aksoy, Julieta Aprea, Lawrence W. Stanton, Sara Bragado Alonso, Philipp Kaldis, Federico Calegari, Shuhui Lim, Akshay Bhinge |
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| Přispěvatelé: | Lee Kong Chian School of Medicine (LKCMedicine) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Neurogenesis Cellular differentiation Biology Models Biological Mice Phosphoserine 03 medical and health sciences chemistry.chemical_compound stomatognathic system Neural Stem Cells Cyclin-dependent kinase Animals Amino Acid Sequence Phosphorylation Kinase activity Molecular Biology Neurons Neural stem cells Protein Stability Kinase SOXB1 Transcription Factors Cell Differentiation DNA Cell Biology Cyclin-Dependent Kinases Neural stem cell Cell biology 030104 developmental biology Gene Expression Regulation chemistry embryonic structures NIH 3T3 Cells biology.protein Mutant Proteins Serine Proteases biological phenomena cell phenomena and immunity Cell cycle regulation Protein Binding Research Article |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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