CIP2A increases self-renewal and is linked to Myc in neural progenitor cells.
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.
Kerosuo
Laura
L
Medical Biochemistry and Developmental Biology, Institute of Biomedicine, University of Helsinki, Helsinki, Finland.
Fox
Heli
H
Perälä
Nina
N
Ahlqvist
Kati
K
Suomalainen
Anu
A
Westermarck
Jukka
J
Sariola
Hannu
H
Wartiovaara
Kirmo
K
D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D004622:Embryo, Mammalian / Q000166:cytology* / Q000378:metabolism; D047108:Embryonic Development; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D012038:Regeneration; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001324:Autoantigens; C500266:CIP2A protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D034741:RNA, Small Interfering