Cyclin-Dependent Kinase-Dependent Phosphorylation of Sox2 at Serine 39 Regulates Neurogenesis

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
Other Titles:
Molecular and Cellular Biology
Keywords:
Publication Date:
28 July 2017
Citation:
Cyclin-Dependent Kinase-Dependent Phosphorylation of Sox2 at Serine 39 Regulates Neurogenesis Shuhui Lim, Akshay Bhinge, Sara Bragado Alonso, Irene Aksoy, Julieta Aprea, Chit Fang Cheok, Federico Calegari, Lawrence W. Stanton, Philipp Kaldis Molecular and Cellular Biology Jul 2017, 37 (16) e00201-17; DOI: 10.1128/MCB.00201-17
Abstract:
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.
License type:
http://creativecommons.org/licenses/by-nc-nd/4.0/
Funding Info:
We deeply appreciate the support and encouragement provided by all members of the Kaldis lab. We thank June Wang, Vithya Anantaraja, and Chloe Sim for help with animal care, Sheena Wee and Jayantha Gunaratne for mass spectrometry, Jiaxuan Chen for ChIP-sequencing, Calista K. L. Ng, Ralf Jauch, and Prasanna R. Kolatkar for EMSA, Araki Marito for the in vitro ubiquitylation assay, Xavier Bisteau for help with the preparation of the final figures, and Wei Theng Poh for chromatin extraction. We acknowledge the technical expertise provided by the Advanced Molecular Pathology Laboratory at IMCB. The authors contributed to this article as follows: S.L., conception and design, collection and/or assembly of data, data analysis and interpretation, and manuscript writing; A.B., I.A., and L.W.S., data collection, data analysis, and interpretation for ChIP-sequencing; J.A., S.B.A., and F.C., data collection, data analysis and interpretation, and manuscript writing for in vivo mouse brain electroporation; C.F.C., discussion; P.K., conception and design, data analysis and interpretation, manuscript writing, financial support, and direction of the study. This work was supported by the Biomedical Research Council of A*STAR (Agency for Science, Technology and Research), Singapore. We declare that we have no competing interests. All data needed to evaluate the conclusions in this paper are presented here. Additional data related to this work may be requested from the authors.
Description:
ISSN:
0270-7306
1098-5549
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