Mimicking p14ARF Phosphorylation Influences Its Ability to Restrain Cell Proliferation
The INK4a/ARF locus on the short arm of chromosome 9 is one of the most frequently altered loci in human cancer. It is generally accepted that ARF is involved in oncogenic checkpoint pathways by sensitizing incipient cancer cells to undergo growth arrest or apoptosis through both p53-dependent and i...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3538741/ https://www.ncbi.nlm.nih.gov/pubmed/23308265 http://dx.doi.org/10.1371/journal.pone.0053631 |
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author | Vivo, Maria Ranieri, Michela Sansone, Federica Santoriello, Cristina Calogero, Raffaele A. Calabrò, Viola Pollice, Alessandra La Mantia, Girolama |
author_facet | Vivo, Maria Ranieri, Michela Sansone, Federica Santoriello, Cristina Calogero, Raffaele A. Calabrò, Viola Pollice, Alessandra La Mantia, Girolama |
author_sort | Vivo, Maria |
collection | PubMed |
description | The INK4a/ARF locus on the short arm of chromosome 9 is one of the most frequently altered loci in human cancer. It is generally accepted that ARF is involved in oncogenic checkpoint pathways by sensitizing incipient cancer cells to undergo growth arrest or apoptosis through both p53-dependent and independent pathways. While intensive studies have been focused on ARF activation at the transcriptional level, only recently mechanisms governing ARF turnover have been identified. Here, we show for the first time that p14ARF is a PKC target. Prediction analysis showed many potential phosphorylation sites in PKC consensus sequences within ARF protein, and, among them, the threonine at position 8 was the most conserved. Substitution of this threonine influences both ARF stability and localization. Furthermore, a phosphomimetic ARF mutation reduces the ability to arrest cell growth although the ability to bind MDM2 and stabilize p53 result unaffected. Thus we propose that phosphorylation of ARF in both immortalized and tumor cell lines could be a mechanism to escape ARF surveillance following proliferative and oncogenic stress. |
format | Online Article Text |
id | pubmed-3538741 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35387412013-01-10 Mimicking p14ARF Phosphorylation Influences Its Ability to Restrain Cell Proliferation Vivo, Maria Ranieri, Michela Sansone, Federica Santoriello, Cristina Calogero, Raffaele A. Calabrò, Viola Pollice, Alessandra La Mantia, Girolama PLoS One Research Article The INK4a/ARF locus on the short arm of chromosome 9 is one of the most frequently altered loci in human cancer. It is generally accepted that ARF is involved in oncogenic checkpoint pathways by sensitizing incipient cancer cells to undergo growth arrest or apoptosis through both p53-dependent and independent pathways. While intensive studies have been focused on ARF activation at the transcriptional level, only recently mechanisms governing ARF turnover have been identified. Here, we show for the first time that p14ARF is a PKC target. Prediction analysis showed many potential phosphorylation sites in PKC consensus sequences within ARF protein, and, among them, the threonine at position 8 was the most conserved. Substitution of this threonine influences both ARF stability and localization. Furthermore, a phosphomimetic ARF mutation reduces the ability to arrest cell growth although the ability to bind MDM2 and stabilize p53 result unaffected. Thus we propose that phosphorylation of ARF in both immortalized and tumor cell lines could be a mechanism to escape ARF surveillance following proliferative and oncogenic stress. Public Library of Science 2013-01-07 /pmc/articles/PMC3538741/ /pubmed/23308265 http://dx.doi.org/10.1371/journal.pone.0053631 Text en © 2013 Vivo 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Vivo, Maria Ranieri, Michela Sansone, Federica Santoriello, Cristina Calogero, Raffaele A. Calabrò, Viola Pollice, Alessandra La Mantia, Girolama Mimicking p14ARF Phosphorylation Influences Its Ability to Restrain Cell Proliferation |
title | Mimicking p14ARF Phosphorylation Influences Its Ability to Restrain Cell Proliferation |
title_full | Mimicking p14ARF Phosphorylation Influences Its Ability to Restrain Cell Proliferation |
title_fullStr | Mimicking p14ARF Phosphorylation Influences Its Ability to Restrain Cell Proliferation |
title_full_unstemmed | Mimicking p14ARF Phosphorylation Influences Its Ability to Restrain Cell Proliferation |
title_short | Mimicking p14ARF Phosphorylation Influences Its Ability to Restrain Cell Proliferation |
title_sort | mimicking p14arf phosphorylation influences its ability to restrain cell proliferation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3538741/ https://www.ncbi.nlm.nih.gov/pubmed/23308265 http://dx.doi.org/10.1371/journal.pone.0053631 |
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