article
KDM2B regulates choline kinase expression and neuronal differentiation of neuroblastoma cells
Autor
Domizi, Pablo
Malizia, Florencia
Chazarreta-Cifre, Lorena
Diacovich, Lautaro
Banchio, Claudia
Institución
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. Para citar este articulo: Domizi P, Malizia F, Chazarreta-Cifre L,
Diacovich L, Banchio C (2019) KDM2B regulates
choline kinase expression and neuronal
differentiation of neuroblastoma cells. PLoS ONE
14(1): e0210207. https://doi.org/10.1371/journal.
pone.0210207 Fil: Domizi, Pablo. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR -CONICET); Argentina. Fil: Malizia, Florencia. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR -CONICET); Argentina. Fil: Chazarreta-Cifre, Lorena. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR -CONICET); Argentina. Fil: Diacovich, Lautaro. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR -CONICET); Argentina. Fil: Banchio, Claudia. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR -CONICET); Argentina.