Abstract
Background. The SCFskp2complex is an E3 ubiquitin ligase that is known to target a number of cell cycle regulators, including cyclin-dependent kinase inhibitors, for proteolysis. While its role in regulation of cell division has been well documented, additional functions in differentiation, including in the nervous system, have not been investigated. Results. Using Xenopus as a model system, here we demonstrate that skp2 has an additional role in regulation of differentiation of primary neurons, the first neurons to differentiate in the neural plate. Xenopus skp2 shows a dynamic expression pattern in early embryonic neural tissue and depletion of skp2 results in generation of extra primary neurons. In contrast, over-expression of skp2 inhibits neurogenesis in a manner dependent on its ability to act as part of the SCFskp2complex. Moreover, inhibition of neurogenesis by skp2 occurs upstream of the proneural gene encoding NeuroD and prior to cell cycle exit. We have previously demonstrated that the Xenopus cyclin dependent kinase inhibitor Xic1 is essential for primary neurogenesis at an early stage, and before these cells exit the cell cycle. We show that SCFskp2degrades Xic1 in embryos and this contributes to the ability of skp2 to regulate neurogenesis. Conclusion. We conclude that the SCFskp2complex has functions in the control of neuronal differentiation additional to its role in cell cycle regulation. Thus, it is well placed to be a co-ordinating factor regulating both cell proliferation and cell differentiation directly.
| Original language | English (US) |
|---|---|
| Article number | 27 |
| Journal | Neural Development |
| Volume | 2 |
| Issue number | 1 |
| DOIs | |
| State | Published - 2007 |
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ASJC Scopus subject areas
- Developmental Neuroscience
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The E3 ubiquitin ligase skp2 regulates neural differentiation independent from the cell cycle. / Boix-Perales, Hector; Horan, Ian; Wise, Helen; Lin, Horng Ru; Chuang, Li Chiou; Yew, Patricia R; Philpott, Anna.
In: Neural Development, Vol. 2, No. 1, 27, 2007.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The E3 ubiquitin ligase skp2 regulates neural differentiation independent from the cell cycle
AU - Boix-Perales, Hector
AU - Horan, Ian
AU - Wise, Helen
AU - Lin, Horng Ru
AU - Chuang, Li Chiou
AU - Yew, Patricia R
AU - Philpott, Anna
PY - 2007
Y1 - 2007
N2 - Background. The SCFskp2complex is an E3 ubiquitin ligase that is known to target a number of cell cycle regulators, including cyclin-dependent kinase inhibitors, for proteolysis. While its role in regulation of cell division has been well documented, additional functions in differentiation, including in the nervous system, have not been investigated. Results. Using Xenopus as a model system, here we demonstrate that skp2 has an additional role in regulation of differentiation of primary neurons, the first neurons to differentiate in the neural plate. Xenopus skp2 shows a dynamic expression pattern in early embryonic neural tissue and depletion of skp2 results in generation of extra primary neurons. In contrast, over-expression of skp2 inhibits neurogenesis in a manner dependent on its ability to act as part of the SCFskp2complex. Moreover, inhibition of neurogenesis by skp2 occurs upstream of the proneural gene encoding NeuroD and prior to cell cycle exit. We have previously demonstrated that the Xenopus cyclin dependent kinase inhibitor Xic1 is essential for primary neurogenesis at an early stage, and before these cells exit the cell cycle. We show that SCFskp2degrades Xic1 in embryos and this contributes to the ability of skp2 to regulate neurogenesis. Conclusion. We conclude that the SCFskp2complex has functions in the control of neuronal differentiation additional to its role in cell cycle regulation. Thus, it is well placed to be a co-ordinating factor regulating both cell proliferation and cell differentiation directly.
AB - Background. The SCFskp2complex is an E3 ubiquitin ligase that is known to target a number of cell cycle regulators, including cyclin-dependent kinase inhibitors, for proteolysis. While its role in regulation of cell division has been well documented, additional functions in differentiation, including in the nervous system, have not been investigated. Results. Using Xenopus as a model system, here we demonstrate that skp2 has an additional role in regulation of differentiation of primary neurons, the first neurons to differentiate in the neural plate. Xenopus skp2 shows a dynamic expression pattern in early embryonic neural tissue and depletion of skp2 results in generation of extra primary neurons. In contrast, over-expression of skp2 inhibits neurogenesis in a manner dependent on its ability to act as part of the SCFskp2complex. Moreover, inhibition of neurogenesis by skp2 occurs upstream of the proneural gene encoding NeuroD and prior to cell cycle exit. We have previously demonstrated that the Xenopus cyclin dependent kinase inhibitor Xic1 is essential for primary neurogenesis at an early stage, and before these cells exit the cell cycle. We show that SCFskp2degrades Xic1 in embryos and this contributes to the ability of skp2 to regulate neurogenesis. Conclusion. We conclude that the SCFskp2complex has functions in the control of neuronal differentiation additional to its role in cell cycle regulation. Thus, it is well placed to be a co-ordinating factor regulating both cell proliferation and cell differentiation directly.
UR - http://www.scopus.com/inward/record.url?scp=38949123365&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=38949123365&partnerID=8YFLogxK
U2 - 10.1186/1749-8104-2-27
DO - 10.1186/1749-8104-2-27
M3 - Article
C2 - 18081928
AN - SCOPUS:38949123365
VL - 2
JO - Neural Development
JF - Neural Development
SN - 1749-8104
IS - 1
M1 - 27
ER -