A high resolution genomic portrait of bladder cancer: correlation between genomic aberrations and the DNA damage response

Article Article scientifique Article A high resolution genomic portrait of bladder cancer: correlation between genomic aberrations and the DNA damage response eng 2012-08-27 2012-08-27 author Schepeler T. author Lamy Paul 822520 author Hvidberg V. author Laurberg J.R. author Fristrup N. author Reinert T. author Bartkova J. author Tropia Laurence 116996 Département de biologie moléculaire et cellulaire (MOCEL) author Bartek J. author Halazonetis Thanos 641033 Département de biologie moléculaire et cellulaire (MOCEL) author Pan C-C. author Borre M. author Dyrskjøt L. author Ørntoft T.F. 3577-3586 10.1038/onc.2012.381 22926521 0950-9232 https://www.nature.com/articles/onc2012381 <p>The DNA damage response (DDR) pathway and ARF function as barriers to cancer development. Although commonly regarded as operating independently of each other, some studies proposed that ARF is positively regulated by the DDR. Contrary to either scenario, we found that in human oncogene-transformed and cancer cells, ATM suppressed ARF protein levels and activity in a transcription-independent manner. Mechanistically, ATM activated protein phosphatase 1, which antagonized Nek2-dependent phosphorylation of nucleophosmin (NPM), thereby liberating ARF from NPM and rendering it susceptible to degradation by the ULF E3-ubiquitin ligase. In human clinical samples, loss of ATM expression correlated with increased ARF levels and in xenograft and tissue culture models, inhibition of ATM stimulated the tumour-suppressive effects of ARF. These results provide insights into the functional interplay between the DDR and ARF anti-cancer barriers, with implications for tumorigenesis and treatment of advanced tumours.</p> Dewey 540 Dewey 570 43 Département de biologie moléculaire 161 39 Département de biochimie 144 false Oncogene 32 31 8e3a8130-f4e5-4a8c-94a3-ce651a03311e Article (Published version) Restricted Article-scientifique-from-crossref.pdf 3040321 application/pdf fb78532bad8816e578cc7451fd3020680c211f6740389a014ab5ca311e956aec restrictedAccess Faculté des sciences / Section de biologie / Département de biologie moléculaire Faculté des sciences / Section de chimie et biochimie / Département de biochimie

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A high resolution genomic portrait of bladder cancer: correlation between genomic aberrations and the DNA damage response	Oncogene			2012	79	0

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Lamy, Paul