GLS2 is transcriptionally regulated by p73 and contributes to neuronal differentiation
Identifieur interne : 000D69 ( Main/Exploration ); précédent : 000D68; suivant : 000D70GLS2 is transcriptionally regulated by p73 and contributes to neuronal differentiation
Auteurs : Tania Velletri [Royaume-Uni, République populaire de Chine] ; Francesco Romeo [Italie] ; Paola Tucci [Royaume-Uni, Italie] ; Angelo Peschiaroli [Italie] ; Margherita Annicchiarico-Petruzzelli [Italie] ; Maria Victoria Niklison-Chirou [Royaume-Uni] ; Ivano Amelio [Royaume-Uni] ; Richard A. Knight [Royaume-Uni] ; Tak W. Mak [Canada] ; Gerry Melino [Royaume-Uni, Italie] ; Massimiliano Agostini [Royaume-Uni]Source :
- Cell Cycle [ 1538-4101 ] ; 2013.
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.
Url:
DOI: 10.4161/cc.26771
PubMed: 24121663
PubMed Central: 3906342
Affiliations:
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Mak</name><affiliation wicri:level="1"><nlm:aff id="A7">The Campbell Family Institute for Breast Cancer Research; Princess Margaret Hospital; Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>The Campbell Family Institute for Breast Cancer Research; Princess Margaret Hospital; Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Melino, Gerry" sort="Melino, Gerry" uniqKey="Melino G" first="Gerry" last="Melino">Gerry Melino</name><affiliation wicri:level="1"><nlm:aff id="A1">Medical Research Council; Toxicology Unit; Leicester University; Leicester, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Medical Research Council; Toxicology Unit; Leicester University; Leicester</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A6">Biochemistry Laboratory IDI-IRCC; Department of Experimental Medicine and Surgery; University of Rome “Tor Vergata”; 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Toxicology Unit; Leicester University; Leicester, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Medical Research Council; Toxicology Unit; Leicester University; Leicester</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">Institute of Health Sciences; Shanghai Institutes for Biological Sciences; Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine; Shanghai, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Institute of Health Sciences; Shanghai Institutes for Biological Sciences; Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine; Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="Romeo, Francesco" sort="Romeo, Francesco" uniqKey="Romeo F" first="Francesco" last="Romeo">Francesco Romeo</name><affiliation wicri:level="1"><nlm:aff id="A3">Department of Experimental and Clinical Medicine; Magna Græcia University of Catanzaro; Catanzaro, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Experimental and Clinical Medicine; Magna Græcia University of Catanzaro; Catanzaro</wicri:regionArea></affiliation></author><author><name sortKey="Tucci, Paola" sort="Tucci, Paola" uniqKey="Tucci P" first="Paola" last="Tucci">Paola Tucci</name><affiliation wicri:level="1"><nlm:aff id="A1">Medical Research Council; Toxicology Unit; Leicester University; Leicester, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Medical Research Council; Toxicology Unit; Leicester University; Leicester</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A4">Department of Pharmaco-Biology; University of Calabria; Rende, Cosenza, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Pharmaco-Biology; University of Calabria; Rende, Cosenza</wicri:regionArea><wicri:noRegion>Cosenza</wicri:noRegion></affiliation></author><author><name sortKey="Peschiaroli, Angelo" sort="Peschiaroli, Angelo" uniqKey="Peschiaroli A" first="Angelo" last="Peschiaroli">Angelo Peschiaroli</name><affiliation wicri:level="1"><nlm:aff id="A5">Institute of Cellular Biology and Neurobiology; CNR; Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Institute of Cellular Biology and Neurobiology; CNR; Rome</wicri:regionArea></affiliation></author><author><name sortKey="Annicchiarico Petruzzelli, Margherita" sort="Annicchiarico Petruzzelli, Margherita" uniqKey="Annicchiarico Petruzzelli M" first="Margherita" last="Annicchiarico-Petruzzelli">Margherita Annicchiarico-Petruzzelli</name><affiliation wicri:level="1"><nlm:aff id="A6">Biochemistry Laboratory IDI-IRCC; Department of Experimental Medicine and Surgery; University of Rome “Tor Vergata”; Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Biochemistry Laboratory IDI-IRCC; Department of Experimental Medicine and Surgery; University of Rome “Tor Vergata”; Rome</wicri:regionArea></affiliation></author><author><name sortKey="Niklison Chirou, Maria Victoria" sort="Niklison Chirou, Maria Victoria" uniqKey="Niklison Chirou M" first="Maria Victoria" last="Niklison-Chirou">Maria Victoria Niklison-Chirou</name><affiliation wicri:level="1"><nlm:aff id="A1">Medical Research Council; Toxicology Unit; Leicester University; Leicester, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Medical Research Council; Toxicology Unit; Leicester University; Leicester</wicri:regionArea></affiliation></author><author><name sortKey="Amelio, Ivano" sort="Amelio, Ivano" uniqKey="Amelio I" first="Ivano" last="Amelio">Ivano Amelio</name><affiliation wicri:level="1"><nlm:aff id="A1">Medical Research Council; Toxicology Unit; Leicester University; Leicester, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Medical Research Council; Toxicology Unit; Leicester University; Leicester</wicri:regionArea></affiliation></author><author><name sortKey="Knight, Richard A" sort="Knight, Richard A" uniqKey="Knight R" first="Richard A" last="Knight">Richard A. Knight</name><affiliation wicri:level="1"><nlm:aff id="A1">Medical Research Council; Toxicology Unit; Leicester University; Leicester, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Medical Research Council; Toxicology Unit; Leicester University; Leicester</wicri:regionArea></affiliation></author><author><name sortKey="Mak, Tak W" sort="Mak, Tak W" uniqKey="Mak T" first="Tak W" last="Mak">Tak W. Mak</name><affiliation wicri:level="1"><nlm:aff id="A7">The Campbell Family Institute for Breast Cancer Research; Princess Margaret Hospital; Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>The Campbell Family Institute for Breast Cancer Research; Princess Margaret Hospital; Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Melino, Gerry" sort="Melino, Gerry" uniqKey="Melino G" first="Gerry" last="Melino">Gerry Melino</name><affiliation wicri:level="1"><nlm:aff id="A1">Medical Research Council; Toxicology Unit; Leicester University; Leicester, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Medical Research Council; Toxicology Unit; Leicester University; Leicester</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A6">Biochemistry Laboratory IDI-IRCC; Department of Experimental Medicine and Surgery; University of Rome “Tor Vergata”; Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Biochemistry Laboratory IDI-IRCC; Department of Experimental Medicine and Surgery; University of Rome “Tor Vergata”; Rome</wicri:regionArea></affiliation></author><author><name sortKey="Agostini, Massimiliano" sort="Agostini, Massimiliano" uniqKey="Agostini M" first="Massimiliano" last="Agostini">Massimiliano Agostini</name><affiliation wicri:level="1"><nlm:aff id="A1">Medical Research Council; Toxicology Unit; Leicester University; Leicester, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Medical Research Council; Toxicology Unit; Leicester University; Leicester</wicri:regionArea></affiliation></author></analytic><series><title level="j">Cell Cycle</title><idno type="ISSN">1538-4101</idno><idno type="eISSN">1551-4005</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>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.</p></div></front></TEI><affiliations><list><country><li>Canada</li><li>Italie</li><li>Royaume-Uni</li><li>République populaire de Chine</li></country></list><tree><country name="Royaume-Uni"><noRegion><name sortKey="Velletri, Tania" sort="Velletri, Tania" uniqKey="Velletri T" first="Tania" last="Velletri">Tania Velletri</name></noRegion><name sortKey="Agostini, Massimiliano" sort="Agostini, Massimiliano" uniqKey="Agostini M" first="Massimiliano" last="Agostini">Massimiliano Agostini</name><name sortKey="Amelio, Ivano" sort="Amelio, Ivano" uniqKey="Amelio I" first="Ivano" last="Amelio">Ivano Amelio</name><name sortKey="Knight, Richard A" sort="Knight, Richard A" uniqKey="Knight R" first="Richard A" last="Knight">Richard A. Knight</name><name sortKey="Melino, Gerry" sort="Melino, Gerry" uniqKey="Melino G" first="Gerry" last="Melino">Gerry Melino</name><name sortKey="Niklison Chirou, Maria Victoria" sort="Niklison Chirou, Maria Victoria" uniqKey="Niklison Chirou M" first="Maria Victoria" last="Niklison-Chirou">Maria Victoria Niklison-Chirou</name><name sortKey="Tucci, Paola" sort="Tucci, Paola" uniqKey="Tucci P" first="Paola" last="Tucci">Paola Tucci</name></country><country name="République populaire de Chine"><noRegion><name sortKey="Velletri, Tania" sort="Velletri, Tania" uniqKey="Velletri T" first="Tania" last="Velletri">Tania Velletri</name></noRegion></country><country name="Italie"><noRegion><name sortKey="Romeo, Francesco" sort="Romeo, Francesco" uniqKey="Romeo F" first="Francesco" last="Romeo">Francesco Romeo</name></noRegion><name sortKey="Annicchiarico Petruzzelli, Margherita" sort="Annicchiarico Petruzzelli, Margherita" uniqKey="Annicchiarico Petruzzelli M" first="Margherita" last="Annicchiarico-Petruzzelli">Margherita Annicchiarico-Petruzzelli</name><name sortKey="Melino, Gerry" sort="Melino, Gerry" uniqKey="Melino G" first="Gerry" last="Melino">Gerry Melino</name><name sortKey="Peschiaroli, Angelo" sort="Peschiaroli, Angelo" uniqKey="Peschiaroli A" first="Angelo" last="Peschiaroli">Angelo Peschiaroli</name><name sortKey="Tucci, Paola" sort="Tucci, Paola" uniqKey="Tucci P" first="Paola" last="Tucci">Paola Tucci</name></country><country name="Canada"><noRegion><name sortKey="Mak, Tak W" sort="Mak, Tak W" uniqKey="Mak T" first="Tak W" last="Mak">Tak W. 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