info:eu-repo/semantics/article
KDM2B regulates choline kinase expression and neuronal differentiation of neuroblastoma cells
Fecha
2019-01Registro en:
Domizi, Pablo Daniel; Malizia, Florencia; Chazarreta Cifré, Lorena Susana; Diacovich, Lautaro; Banchio, Claudia Elena; KDM2B regulates choline kinase expression and neuronal differentiation of neuroblastoma cells; Public Library of Science; Plos One; 14; 1; 1-2019; 1-15
1932-6203
CONICET Digital
CONICET
Autor
Domizi, Pablo Daniel
Malizia, Florencia
Chazarreta Cifré, Lorena Susana
Diacovich, Lautaro
Banchio, Claudia Elena
Resumen
The process of neuronal differentiation is associated with neurite elongation and membrane biogenesis, and phosphatidylcholine (PtdCho) is the major membrane phospholipid in mammalian cells. During neuroblast differentiation, the transcription of two genes involved in PtdCho biosynthesis are stimulated: Chka gene for choline kinase (CK) alpha isoform and Pcyt1a gene for CTP:phosphocholine cytidylyltransferase (CCT) alpha isoform. Here we show that CKα is essential for neuronal differentiation. In addition, we demonstrated that KDM2B regulates CKα expression and, as a consequence, neuronal differentiation. This factor is up-regulated in the course of the neuroblasts proliferative and undifferentiated state and down-regulated during differentiation induced by retinoic acid (RA). During proliferation, KDM2B binds to the Box2 located in the Chka promoter repressing its transcription. Interestingly, KDM2B knockdown enhances the levels of CKα expression in neuroblast cells and induces neuronal differentiation even in the absence of RA. These results suggest that KDM2B is required for the appropriate regulation of CKα during neuronal differentiation and to the maintaining of the undifferentiated stage of neuroblast cells.