PKC Dependent p14ARF Phosphorylation on Threonine 8 Drives Cell Proliferation

Abstract ARF role as tumor suppressor has been challenged in the last years by several findings of different groups ultimately showing that its functions can be strictly context dependent. We previously showed that ARF loss in HeLa cells induces spreading defects, evident as rounded morphology of de...

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Autores principales:	Rosa Fontana, Daniela Guidone, Felicia Sangermano, Viola Calabrò, Alessandra Pollice, Girolama La Mantia, Maria Vivo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6cd4bd4f9ec14992b6f77943445572ad
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spelling	oai:doaj.org-article:6cd4bd4f9ec14992b6f77943445572ad2021-12-02T15:08:55ZPKC Dependent p14ARF Phosphorylation on Threonine 8 Drives Cell Proliferation10.1038/s41598-018-25496-42045-2322https://doaj.org/article/6cd4bd4f9ec14992b6f77943445572ad2018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25496-4https://doaj.org/toc/2045-2322Abstract ARF role as tumor suppressor has been challenged in the last years by several findings of different groups ultimately showing that its functions can be strictly context dependent. We previously showed that ARF loss in HeLa cells induces spreading defects, evident as rounded morphology of depleted cells, accompanied by a decrease of phosphorylated Focal Adhesion Kinase (FAK) protein levels and anoikis. These data, together with previous finding that a PKC dependent signalling pathway can lead to ARF stabilization, led us to the hypothesis that ARF functions in cell proliferation might be regulated by phosphorylation. In line with this, we show here that upon spreading ARF is induced through PKC activation. A constitutive-phosphorylated ARF mutant on the conserved threonine 8 (T8D) is able to mediate both cell spreading and FAK activation. Finally, ARF-T8D expression confers growth advantage to cells thus leading to the intriguing hypothesis that ARF phosphorylation could be a mechanism through which pro-proliferative or anti proliferative signals could be transduced inside the cells in both physiological and pathological conditions.Rosa FontanaDaniela GuidoneFelicia SangermanoViola CalabròAlessandra PolliceGirolama La MantiaMaria VivoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rosa Fontana Daniela Guidone Felicia Sangermano Viola Calabrò Alessandra Pollice Girolama La Mantia Maria Vivo PKC Dependent p14ARF Phosphorylation on Threonine 8 Drives Cell Proliferation
description	Abstract ARF role as tumor suppressor has been challenged in the last years by several findings of different groups ultimately showing that its functions can be strictly context dependent. We previously showed that ARF loss in HeLa cells induces spreading defects, evident as rounded morphology of depleted cells, accompanied by a decrease of phosphorylated Focal Adhesion Kinase (FAK) protein levels and anoikis. These data, together with previous finding that a PKC dependent signalling pathway can lead to ARF stabilization, led us to the hypothesis that ARF functions in cell proliferation might be regulated by phosphorylation. In line with this, we show here that upon spreading ARF is induced through PKC activation. A constitutive-phosphorylated ARF mutant on the conserved threonine 8 (T8D) is able to mediate both cell spreading and FAK activation. Finally, ARF-T8D expression confers growth advantage to cells thus leading to the intriguing hypothesis that ARF phosphorylation could be a mechanism through which pro-proliferative or anti proliferative signals could be transduced inside the cells in both physiological and pathological conditions.
format	article
author	Rosa Fontana Daniela Guidone Felicia Sangermano Viola Calabrò Alessandra Pollice Girolama La Mantia Maria Vivo
author_facet	Rosa Fontana Daniela Guidone Felicia Sangermano Viola Calabrò Alessandra Pollice Girolama La Mantia Maria Vivo
author_sort	Rosa Fontana
title	PKC Dependent p14ARF Phosphorylation on Threonine 8 Drives Cell Proliferation
title_short	PKC Dependent p14ARF Phosphorylation on Threonine 8 Drives Cell Proliferation
title_full	PKC Dependent p14ARF Phosphorylation on Threonine 8 Drives Cell Proliferation
title_fullStr	PKC Dependent p14ARF Phosphorylation on Threonine 8 Drives Cell Proliferation
title_full_unstemmed	PKC Dependent p14ARF Phosphorylation on Threonine 8 Drives Cell Proliferation
title_sort	pkc dependent p14arf phosphorylation on threonine 8 drives cell proliferation
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/6cd4bd4f9ec14992b6f77943445572ad
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PKC Dependent p14ARF Phosphorylation on Threonine 8 Drives Cell Proliferation

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