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...
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2013
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oai:doaj.org-article:df5c53d8a51143d1a153337ebf085b9b2021-11-18T08:02:26ZMimicking p14ARF phosphorylation influences its ability to restrain cell proliferation.1932-620310.1371/journal.pone.0053631https://doaj.org/article/df5c53d8a51143d1a153337ebf085b9b2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23308265/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The 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.Maria VivoMichela RanieriFederica SansoneCristina SantorielloRaffaele A CalogeroViola CalabròAlessandra PolliceGirolama La MantiaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e53631 (2013) |
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DOAJ |
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Medicine R Science Q |
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Medicine R Science Q Maria Vivo Michela Ranieri Federica Sansone Cristina Santoriello Raffaele A Calogero Viola Calabrò Alessandra Pollice Girolama La Mantia Mimicking p14ARF phosphorylation influences its ability to restrain cell proliferation. |
| 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 |
article |
| author |
Maria Vivo Michela Ranieri Federica Sansone Cristina Santoriello Raffaele A Calogero Viola Calabrò Alessandra Pollice Girolama La Mantia |
| author_facet |
Maria Vivo Michela Ranieri Federica Sansone Cristina Santoriello Raffaele A Calogero Viola Calabrò Alessandra Pollice Girolama La Mantia |
| author_sort |
Maria Vivo |
| title |
Mimicking p14ARF phosphorylation influences its ability to restrain cell proliferation. |
| title_short |
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_sort |
mimicking p14arf phosphorylation influences its ability to restrain cell proliferation. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/df5c53d8a51143d1a153337ebf085b9b |
| work_keys_str_mv |
AT mariavivo mimickingp14arfphosphorylationinfluencesitsabilitytorestraincellproliferation AT michelaranieri mimickingp14arfphosphorylationinfluencesitsabilitytorestraincellproliferation AT federicasansone mimickingp14arfphosphorylationinfluencesitsabilitytorestraincellproliferation AT cristinasantoriello mimickingp14arfphosphorylationinfluencesitsabilitytorestraincellproliferation AT raffaeleacalogero mimickingp14arfphosphorylationinfluencesitsabilitytorestraincellproliferation AT violacalabro mimickingp14arfphosphorylationinfluencesitsabilitytorestraincellproliferation AT alessandrapollice mimickingp14arfphosphorylationinfluencesitsabilitytorestraincellproliferation AT girolamalamantia mimickingp14arfphosphorylationinfluencesitsabilitytorestraincellproliferation |
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1718422636948619264 |