GLS2 is transcriptionally regulated by p73 and contributes to neuronal differentiation

Tania Velletri, Francesco Romeo, Paola Tucci, Angelo Peschiaroli, Margherita Annicchiarico-Petruzzelli, Maria Victoria Niklison-Chirou, Ivano Amelio, Richard A. Knight, Tak W. Mak, Gerry Melino, Massimiliano Agostini

Research output: Contribution to journalArticle

Abstract

The amino acid Glutamine is converted into Glutamate by a deamidation reaction catalyzed by the enzyme Glutaminase (GLS). Two isoforms of this enzyme have been described, and the GLS2 isoform is regulated by the tumor suppressor gene p53. Here, we show that the p53 family member TAp73 also drives the expression of GLS2. Specifically, we demonstrate that TAp73 regulates GLS2 during retinoic acid-induced terminal neuronal differentiation of neuroblastoma cells, and overexpression or inhibition of GLS2 modulates neuronal differentiation and intracellular levels of ATP . Moreover, inhibition of GLS activity, by removing Glutamine from the growth medium, impairs in vitro differentiation of cortical neurons. Finally, expression of GLS2 increases during mouse cerebellar development. Although, p73 is dispensable for the in vivo expression of GLS2, TAp73 loss affects GABA and Glutamate levels in cortical neurons. Together, these findings suggest a role for GLS2 acting, at least in part, downstream of p73 in neuronal differentiation and highlight a possible role of p73 in regulating neurotransmitter synthesis.

Original languageEnglish
Pages (from-to)3564-3573
Number of pages10
JournalCell Cycle
Volume12
Issue number22
DOIs
Publication statusPublished - Nov 15 2013

Keywords

  • Apoptosis
  • GLS2
  • Metabolism
  • Neuronal differentiation
  • Neurotransmitter
  • p53 family
  • p73

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

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  • Cite this

    Velletri, T., Romeo, F., Tucci, P., Peschiaroli, A., Annicchiarico-Petruzzelli, M., Niklison-Chirou, M. V., Amelio, I., Knight, R. A., Mak, T. W., Melino, G., & Agostini, M. (2013). GLS2 is transcriptionally regulated by p73 and contributes to neuronal differentiation. Cell Cycle, 12(22), 3564-3573. https://doi.org/10.4161/cc.26771