Disruption of Dnmt1/PCNA/UHRF1 interactions promotes tumorigenesis from human and mice glial cells.
Global DNA hypomethylation is a hallmark of cancer cells, but its molecular mechanisms have not been elucidated. Here, we show that the disruption of Dnmt1/PCNA/UHRF1 interactions promotes a global DNA hypomethylation in human gliomas. We then demonstrate that the Dnmt1 phosphorylations by Akt and/o...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2010-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2894052?pdf=render |
| _version_ | 1818189925374230528 |
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| author | Eric Hervouet Lisenn Lalier Emilie Debien Mathilde Cheray Audrey Geairon Hélène Rogniaux Delphine Loussouarn Stéphane A Martin François M Vallette Pierre-François Cartron |
| author_facet | Eric Hervouet Lisenn Lalier Emilie Debien Mathilde Cheray Audrey Geairon Hélène Rogniaux Delphine Loussouarn Stéphane A Martin François M Vallette Pierre-François Cartron |
| author_sort | Eric Hervouet |
| collection | DOAJ |
| description | Global DNA hypomethylation is a hallmark of cancer cells, but its molecular mechanisms have not been elucidated. Here, we show that the disruption of Dnmt1/PCNA/UHRF1 interactions promotes a global DNA hypomethylation in human gliomas. We then demonstrate that the Dnmt1 phosphorylations by Akt and/or PKC abrogate the interactions of Dnmt1 with PCNA and UHRF1 in cellular and acellular studies including mass spectrometric analyses and the use of primary cultured patient-derived glioma. By using methylated DNA immunoprecipitation, methylation and CGH arrays, we show that global DNA hypomethylation is associated with genes hypomethylation, hypomethylation of DNA repeat element and chromosomal instability. Our results reveal that the disruption of Dnmt1/PCNA/UHRF1 interactions acts as an oncogenic event and that one of its signatures (i.e. the low level of mMTase activity) is a molecular biomarker associated with a poor prognosis in GBM patients. We identify the genetic and epigenetic alterations which collectively promote the acquisition of tumor/glioma traits by human astrocytes and glial progenitor cells as that promoting high proliferation and apoptosis evasion. |
| first_indexed | 2024-12-11T23:50:34Z |
| format | Article |
| id | doaj.art-e6b489b93bb241d5b62847119b29440c |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T23:50:34Z |
| publishDate | 2010-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-e6b489b93bb241d5b62847119b29440c2022-12-22T00:45:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-01-0156e1133310.1371/journal.pone.0011333Disruption of Dnmt1/PCNA/UHRF1 interactions promotes tumorigenesis from human and mice glial cells.Eric HervouetLisenn LalierEmilie DebienMathilde CherayAudrey GeaironHélène RogniauxDelphine LoussouarnStéphane A MartinFrançois M VallettePierre-François CartronGlobal DNA hypomethylation is a hallmark of cancer cells, but its molecular mechanisms have not been elucidated. Here, we show that the disruption of Dnmt1/PCNA/UHRF1 interactions promotes a global DNA hypomethylation in human gliomas. We then demonstrate that the Dnmt1 phosphorylations by Akt and/or PKC abrogate the interactions of Dnmt1 with PCNA and UHRF1 in cellular and acellular studies including mass spectrometric analyses and the use of primary cultured patient-derived glioma. By using methylated DNA immunoprecipitation, methylation and CGH arrays, we show that global DNA hypomethylation is associated with genes hypomethylation, hypomethylation of DNA repeat element and chromosomal instability. Our results reveal that the disruption of Dnmt1/PCNA/UHRF1 interactions acts as an oncogenic event and that one of its signatures (i.e. the low level of mMTase activity) is a molecular biomarker associated with a poor prognosis in GBM patients. We identify the genetic and epigenetic alterations which collectively promote the acquisition of tumor/glioma traits by human astrocytes and glial progenitor cells as that promoting high proliferation and apoptosis evasion.http://europepmc.org/articles/PMC2894052?pdf=render |
| spellingShingle | Eric Hervouet Lisenn Lalier Emilie Debien Mathilde Cheray Audrey Geairon Hélène Rogniaux Delphine Loussouarn Stéphane A Martin François M Vallette Pierre-François Cartron Disruption of Dnmt1/PCNA/UHRF1 interactions promotes tumorigenesis from human and mice glial cells. PLoS ONE |
| title | Disruption of Dnmt1/PCNA/UHRF1 interactions promotes tumorigenesis from human and mice glial cells. |
| title_full | Disruption of Dnmt1/PCNA/UHRF1 interactions promotes tumorigenesis from human and mice glial cells. |
| title_fullStr | Disruption of Dnmt1/PCNA/UHRF1 interactions promotes tumorigenesis from human and mice glial cells. |
| title_full_unstemmed | Disruption of Dnmt1/PCNA/UHRF1 interactions promotes tumorigenesis from human and mice glial cells. |
| title_short | Disruption of Dnmt1/PCNA/UHRF1 interactions promotes tumorigenesis from human and mice glial cells. |
| title_sort | disruption of dnmt1 pcna uhrf1 interactions promotes tumorigenesis from human and mice glial cells |
| url | http://europepmc.org/articles/PMC2894052?pdf=render |
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