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

2017 ◽  
Vol 37 (16) ◽  
Author(s):  
Shuhui Lim ◽  
Akshay Bhinge ◽  
Sara Bragado Alonso ◽  
Irene Aksoy ◽  
Julieta Aprea ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Neuronal Differentiation ◽  
Kinase Activity ◽  
Phosphorylation Site ◽  
Cyclin Dependent Kinase ◽  
Truncated Form ◽  
Self Renewal ◽  
Cdk Phosphorylation

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.

scholarly journals BRCA1 Is Phosphorylated at Serine 1497 In Vivo at a Cyclin-Dependent Kinase 2 Phosphorylation Site

1999 ◽  
Vol 19 (7) ◽  
pp. 4843-4854 ◽  
Author(s):  
Heinz Ruffner ◽  
Wei Jiang ◽  
A. Grey Craig ◽  
Tony Hunter ◽  
Inder M. Verma
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Kinase Activity ◽  
Phosphorylation Site ◽  
Cyclin A ◽  
Dominant Negative ◽  
Protein Kinase Activity ◽  
Cyclin Dependent Kinase

ABSTRACT BRCA1 is a cell cycle-regulated nuclear protein that is phosphorylated mainly on serine and to a lesser extent on threonine residues. Changes in phosphorylation occur in response to cell cycle progression and DNA damage. Specifically, BRCA1 undergoes hyperphosphorylation during late G1 and S phases of the cell cycle. Here we report that BRCA1 is phosphorylated in vivo at serine 1497 (S1497), which is part of a cyclin-dependent kinase (CDK) consensus site. S1497 can be phosphorylated in vitro by CDK2-cyclin A or E. BRCA1 coimmunoprecipitates with an endogenous serine-threonine protein kinase activity that phosphorylates S1497 in vitro. This cellular kinase activity is sensitive to transfection of a dominant negative form of CDK2 as well as the application of the CDK inhibitors p21 and butyrolactone I but not p16. Furthermore, BRCA1 coimmunoprecipitates with CDK2 and cyclin A. These results suggest that the endogenous kinase activity is composed of CDK2-cyclin complexes, at least in part, concordant with the G1/S-specific increase in BRCA1 phosphorylation.

scholarly journals In Vivo Fate Analysis Reveals the Multipotent and Self-Renewal Capacities of Sox2+ Neural Stem Cells in the Adult Hippocampus

2007 ◽  
Vol 1 (5) ◽  
pp. 515-528 ◽  
Author(s):  
Hoonkyo Suh ◽  
Antonella Consiglio ◽  
Jasodhara Ray ◽  
Toru Sawai ◽  
Kevin A. D'Amour ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Self Renewal ◽  
Adult Hippocampus

RGCC balances self‐renewal and neuronal differentiation of neural stem cells in the developing mammalian neocortex

EMBO Reports ◽  
2021 ◽  
Author(s):  
Zhenming Guo ◽  
Mengxia Chen ◽  
Yiming Chao ◽  
Chunhai Cai ◽  
Liangjie Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Neuronal Differentiation ◽  
Self Renewal

scholarly journals MicroRNA-124-loaded nanoparticles increase survival and neuronal differentiation of neural stem cells in vitro but do not contribute to stroke outcome in vivo

PLoS ONE ◽  
2018 ◽  
Vol 13 (3) ◽  
pp. e0193609 ◽  
Author(s):  
Cláudia Saraiva ◽  
Daniela Talhada ◽  
Akhilesh Rai ◽  
Raquel Ferreira ◽  
Lino Ferreira ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Neuronal Differentiation ◽  
Stroke Outcome ◽  
Microrna 124

scholarly journals EphB4 Regulates Self-Renewal, Proliferation and Neuronal Differentiation of Human Embryonic Neural Stem Cells in Vitro

2017 ◽  
Vol 41 (2) ◽  
pp. 819-834 ◽  
Author(s):  
Tingting Liu ◽  
Xianwei Zeng ◽  
Fangling Sun ◽  
Hongli Hou ◽  
Yunqian Guan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Neuronal Differentiation ◽  
Glial Cells ◽  
Tyrosine Kinases ◽  
Fine Tuning ◽  
Brain Diseases ◽  
Self Renewal ◽  
Neuronal Lineage

Background/Aims: EphB4 belongs to the largest family of Eph receptor tyrosine kinases. It contributes to a variety of pathological progresses of cancer malignancy. However, little is known about its role in neural stem cells (NSCs). This study examined whether EphB4 is required for proliferation and differentiation of human embryonic neural stem cells (hNSCs) in vitro. Methods: We up- and down-regulated EphB4 expression in hNSCs using lentiviral over-expression and shRNA knockdown constructs and then investigated the influence of EphB4 on the properties of hNSCs. Results: Our results show that shRNA-mediated EphB4 reduction profoundly impaired hNSCs self-renewal and proliferation. Furthermore, detection of differentiation revealed that knockdown of EphB4 inhibited hNSCs differentiation towards a neuronal lineage and promoted hNSCs differentiation to glial cells. In contrast, EphB4 overexpression promoted hNSCs self-renewal and proliferation, further induced hNSCs differentiation towards a neuronal lineage and inhibited hNSCs differentiation to glial cells. Moreover, we found that EphB4 regulates cell proliferation mediated by the Abl-CyclinD1 pathway. Conclusion: These studies provide strong evidence that fine tuning of EphB4 expression is crucial for the proliferation and neuronal differentiation of hNSCs, suggesting that EphB4 might be an interesting target for overcoming some of the therapeutic limitations of neuronal loss in brain diseases.

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