Cyclin-dependent kinasedependent phosphorylation of Sox2 at serine 39 regulates neurogenesis
Lim, Shuhui ; Bhinge, Akshay ; Alonso, Sara Bragado ; Aksoy, Irene ; Aprea, Julieta ; Cheok, Chit Fang ; Calegari, Federico ; Stanton, Lawrence W. and Kaldis, Philipp LU
(2017)
In Molecular and Cellular Biology
37(16).
- 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... (More)
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.
(Less)
- author
- Lim, Shuhui
; Bhinge, Akshay
; Alonso, Sara Bragado
; Aksoy, Irene
; Aprea, Julieta
; Cheok, Chit Fang
; Calegari, Federico
; Stanton, Lawrence W.
and Kaldis, Philipp
LU
- publishing date
- 2017-08
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Cdks, Cell cycle regulation, Cyclin-dependent kinases, Differentiation, Neural stem cells, Self-renewal, Sox2
- in
- Molecular and Cellular Biology
- volume
- 37
- issue
- 16
- article number
- e00201-17
- publisher
- American Society for Microbiology
- external identifiers
-
- pmid:28584195
- scopus:85026345977
- ISSN
- 0270-7306
- DOI
- 10.1128/MCB.00201-17
- language
- English
- LU publication?
- no
- id
- 4ee20695-8079-4695-9a60-dadaab29acc3
- date added to LUP
- 2019-09-18 10:12:50
- date last changed
- 2024-02-15 21:22:01
@article{4ee20695-8079-4695-9a60-dadaab29acc3,
abstract = {{<p>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.</p>}},
author = {{Lim, Shuhui and Bhinge, Akshay and Alonso, Sara Bragado and Aksoy, Irene and Aprea, Julieta and Cheok, Chit Fang and Calegari, Federico and Stanton, Lawrence W. and Kaldis, Philipp}},
issn = {{0270-7306}},
keywords = {{Cdks; Cell cycle regulation; Cyclin-dependent kinases; Differentiation; Neural stem cells; Self-renewal; Sox2}},
language = {{eng}},
number = {{16}},
publisher = {{American Society for Microbiology}},
series = {{Molecular and Cellular Biology}},
title = {{Cyclin-dependent kinasedependent phosphorylation of Sox2 at serine 39 regulates neurogenesis}},
url = {{http://dx.doi.org/10.1128/MCB.00201-17}},
doi = {{10.1128/MCB.00201-17}},
volume = {{37}},
year = {{2017}},
}