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KDM2B regulates choline kinase expression and neuronal differentiation of neuroblastoma cells

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 stimula...

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Autores principales: Domizi, Pablo, Malizia, Florencia, Chazarreta-Cifre, Lorena, Diacovich, Lautaro, Banchio, Claudia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328129/
https://www.ncbi.nlm.nih.gov/pubmed/30629659
http://dx.doi.org/10.1371/journal.pone.0210207
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author Domizi, Pablo
Malizia, Florencia
Chazarreta-Cifre, Lorena
Diacovich, Lautaro
Banchio, Claudia
author_facet Domizi, Pablo
Malizia, Florencia
Chazarreta-Cifre, Lorena
Diacovich, Lautaro
Banchio, Claudia
author_sort Domizi, Pablo
collection PubMed
description 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.
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spelling pubmed-63281292019-02-01 KDM2B regulates choline kinase expression and neuronal differentiation of neuroblastoma cells Domizi, Pablo Malizia, Florencia Chazarreta-Cifre, Lorena Diacovich, Lautaro Banchio, Claudia PLoS One Research Article 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. Public Library of Science 2019-01-10 /pmc/articles/PMC6328129/ /pubmed/30629659 http://dx.doi.org/10.1371/journal.pone.0210207 Text en © 2019 Domizi et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Domizi, Pablo
Malizia, Florencia
Chazarreta-Cifre, Lorena
Diacovich, Lautaro
Banchio, Claudia
KDM2B regulates choline kinase expression and neuronal differentiation of neuroblastoma cells
title KDM2B regulates choline kinase expression and neuronal differentiation of neuroblastoma cells
title_full KDM2B regulates choline kinase expression and neuronal differentiation of neuroblastoma cells
title_fullStr KDM2B regulates choline kinase expression and neuronal differentiation of neuroblastoma cells
title_full_unstemmed KDM2B regulates choline kinase expression and neuronal differentiation of neuroblastoma cells
title_short KDM2B regulates choline kinase expression and neuronal differentiation of neuroblastoma cells
title_sort kdm2b regulates choline kinase expression and neuronal differentiation of neuroblastoma cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328129/
https://www.ncbi.nlm.nih.gov/pubmed/30629659
http://dx.doi.org/10.1371/journal.pone.0210207
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