Somatic mutations of the Parkinson's disease-associated gene PARK2 in glioblastoma and other human malignancies.

Nature Genetics
Selvaraju VeeriahTimothy A Chan

Abstract

Mutation of the gene PARK2, which encodes an E3 ubiquitin ligase, is the most common cause of early-onset Parkinson's disease. In a search for multisite tumor suppressors, we identified PARK2 as a frequently targeted gene on chromosome 6q25.2-q27 in cancer. Here we describe inactivating somatic mutations and frequent intragenic deletions of PARK2 in human malignancies. The PARK2 mutations in cancer occur in the same domains, and sometimes at the same residues, as the germline mutations causing familial Parkinson's disease. Cancer-specific mutations abrogate the growth-suppressive effects of the PARK2 protein. PARK2 mutations in cancer decrease PARK2's E3 ligase activity, compromising its ability to ubiquitinate cyclin E and resulting in mitotic instability. These data strongly point to PARK2 as a tumor suppressor on 6q25.2-q27. Thus, PARK2, a gene that causes neuronal dysfunction when mutated in the germline, may instead contribute to oncogenesis when altered in non-neuronal somatic cells.

References

Oct 1, 1991·Brain : a Journal of Neurology·J M Fearnley, A J Lees
Jun 10, 1995·BMJ : British Medical Journal·H MøllerJ H Olsen
Apr 5, 1996·Cell·G SozziC M Croce
May 16, 1998·Genome Research·D GordonP Green
May 4, 1999·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·R Donnellan, R Chetty
Sep 28, 1999·Nature·C H SpruckS I Reed
May 20, 2000·Mammalian Genome : Official Journal of the International Mammalian Genome Society·T KitadaN Shimizu
May 29, 2000·The New England Journal of Medicine·C B LückingUNKNOWN European Consortium on Genetic Susceptibility in Parkinson's Disease
Nov 15, 2000·Proceedings of the National Academy of Sciences of the United States of America·Y ZhangT M Dawson
Dec 11, 2002·Journal of Neurochemistry·Maria Dolores LedesmaPoul Henning Jensen
Apr 30, 2003·Proceedings of the National Academy of Sciences of the United States of America·Rossano CesariCarlo M Croce
Aug 26, 2003·Human Mutation·Charis Eng
Feb 12, 2004·Cancer Research·Susanna Ekholm-ReedSusanna Ekholm Reed
Mar 6, 2004·Nature·Harith RajagopalanChristoph Lengauer
Apr 22, 2004·Genes, Chromosomes & Cancer·Fang WangDavid I Smith
Jun 3, 2004·Lancet·Ali SamiiBruce R Ransom
Dec 8, 2004·British Journal of Cancer·J H OlsenH Møller
Jan 5, 2005·Experimental Neurology·Ranjita BetarbetJ Timothy Greenamyre
Mar 12, 2005·Proceedings of the National Academy of Sciences of the United States of America·Charles CoxMichael R Stratton
Mar 18, 2005·Comptes rendus biologies·Olga CortiAlexis Brice
May 27, 2005·Methods in Molecular Biology·Michael G Schlossmacher, Hideki Shimura
Jul 1, 2005·FEBS Letters·J C DächselT Gasser
Dec 15, 2005·Proceedings of the National Academy of Sciences of the United States of America·Wanli W SmithChristopher A Ross
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Steven A BeasleyGary S Shaw
Jun 30, 2007·Bioinformatics·John E Major
Aug 1, 2007·The Journal of Cell Biology·Jamie M KeckSteven I Reed
Nov 6, 2007·Nature·Barbara A WeirMatthew Meyerson
Feb 6, 2008·Journal of Neurochemistry·Darren J MooreTed M Dawson

❮ Previous
Next ❯

Citations

Jul 3, 2013·Seminars in Cancer Biology·Séverine LorinPatrice Codogno
Jul 27, 2012·Nature·Paul A NorthcottMichael D Taylor
Sep 1, 2012·Nature Reviews. Drug Discovery·David C RubinszteinBeth Levine
Oct 10, 2012·Nature Reviews. Genetics·Lucy R Yates, Peter J Campbell
Aug 11, 2010·Proceedings of the National Academy of Sciences of the United States of America·George PoulogiannisMark J Arends
Sep 21, 2011·Proceedings of the National Academy of Sciences of the United States of America·Cen ZhangZhaohui Feng
Nov 1, 2012·Proceedings of the National Academy of Sciences of the United States of America·Keyan SalariJonathan R Pollack
May 30, 2013·Bioinformatics·Laura ToloşiThomas Lengauer
Mar 6, 2012·Human Molecular Genetics·Yeun Su ChooZhuohua Zhang
Feb 1, 2012·The Cancer Journal·Siyuan ZhengRoel G W Verhaak
Jul 4, 2012·Genes & Development·An-Jou ChenRonald A Depinho
Jun 15, 2011·Annals of Human Genetics·Digna R Velez EdwardsWilliam K Scott
Dec 2, 2010·Microbiology and Molecular Biology Reviews : MMBR·Elizabeth A MischThomas R Hawn
May 24, 2012·Oxidative Medicine and Cellular Longevity·Marlene Jimenez-Del-Rio, Carlos Velez-Pardo
Jul 24, 2012·Cell Division·Panagiotis J VlachostergiosChristos N Papandreou
Dec 6, 2012·Translational Neurodegeneration·Brian R HaasJing Zhang
Jan 5, 2011·PLoS Genetics·Hélène Plun-FavreauNicholas W Wood
Jul 19, 2014·PloS One·Melike KorucuogluHasan H Otu
May 6, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sama F SleimanRajiv R Ratan
Oct 31, 2012·International Journal of Molecular Sciences·Ke MaZheng Li
Feb 4, 2014·Genome Medicine·Lisa EversMichael T Barrett
Feb 12, 2014·Antioxidants & Redox Signaling·Rodrigo Portes UreshinoSoraya Soubhi Smaili
May 29, 2014·Nature Genetics·Jiri Bartek, Zdenek Hodny
Jul 7, 2011·Proceedings of the National Academy of Sciences of the United States of America·Christian RuizMichael T Barrett
May 24, 2014·Human Molecular Genetics·Tom CornelissenWim Vandenberghe
Aug 20, 2014·BioMed Research International·Soraya ScuderiVelia D'Agata
Oct 30, 2013·Oncogene·S-M HedeF J Swartling
Oct 11, 2014·Cellular and Molecular Life Sciences : CMLS·Ge Gao, David I Smith
Apr 25, 2012·Cellular and Molecular Life Sciences : CMLS·Helen Walden, R Julio Martinez-Torres
Jan 12, 2011·Pathology Oncology Research : POR·Syed Jafar MehdiM Moshahid Alam Rizvi
Dec 12, 2012·Pathology Oncology Research : POR·Eun Mi JeSug Hyung Lee
Dec 4, 2013·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Liang XuH Phillip Koeffler
May 23, 2012·Molecular Neurobiology·Deepak ChhanganiAmit Mishra
Dec 30, 2015·International Journal of Molecular Sciences·Hueng-Chuen FanHorng-Jyh Harn

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