期刊
DIFFERENTIATION
卷 80, 期 1, 页码 68-77出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.diff.2010.04.003
关键词
CIP2A; Self-renewal; Myc; Neural progenitor cells; Neural stem cells
资金
- Helsinki Biomedical Graduate School, Academy of Finland
- Finnish Cultural Foundation
- Finnish Cancer organisations
- Otto A. Malm Foundation
- K Albin Johansson Foundation
- Orion-Farmos Research Foundation
- Swedish Cultural Foundation in Finland
- Maud Kuistila's Memorial Foundation
- Nona and Kullervo Vare Foundation
The oncogenic transcription factor Myc has an established role in the regulation of stem cell self-renewal and differentiation. However, the regulation of Myc activity or expression in stem and progenitor cells is not thoroughly understood. We studied the expression and function of the Myc stabilizing protein and a newly found oncogene, cancerous inhibitor of protein phosphatase 2A (CIP2A) in mouse neural progenitor cells (NPCs). We found intensive CIP2A expression in the neurogenic areas of the developing E13 as well as of the adult mouse brain. Here we also show that retroviral overexpression of CIP2A increases and siRNA silencing of CIP2A decreases NPC self-renewal and proliferation. Differentiation of the NPCs correlates with diminished CIP2A expression although overexpression of CIP2A does not prevent differentiation of neurons and astrocytes. Lastly, we demonstrate that both Myc and CIP2A enhance each other's expression and siRNA against CIP2A in Myc-overexpressing NPCs significantly reduces the ability of Myc to increase self-renewal and proliferation thus indicating a functional connection between CIP2A and Myc in NPCs. (C) 2010 International Society of Differentiation. Published by Elsevier Ltd. All rights reserved.
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