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The protein phospha...
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van Kempen, Leon C. L.McGill Univ, Dept Pathol, Montreal, PQ, Canada.;Lady Davis Inst Med Res, Montreal, PQ, Canada.
(author)
The protein phosphatase 2A regulatory subunit PR70 is a gonosomal melanoma tumor suppressor gene
- Article/chapterEnglish2016
Publisher, publication year, extent ...
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American Association for the Advancement of Science (AAAS),2016
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-314415
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-314415URI
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https://doi.org/10.1126/scitranslmed.aai9188DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Male gender is independently and significantly associated with poor prognosis in melanoma of all clinical stages. The biological underpinnings of this sex difference remain largely unknown, but we hypothesized that gene expression from gonosomes (sex chromosomes) might play an important role. We demonstrate that loss of the inactivated X chromosome in melanomas arising in females is strongly associated with poor distant metastasis-free survival, suggesting a dosage benefit from two X chromosomes. The gonosomal protein phosphatase 2 regulatory subunit B, beta (PPP2R3B) gene is located on the pseudoautosomal region (PAR) of the X chromosome in females and the Y chromosome in males. We observed that, despite its location on the PAR that predicts equal dosage across genders, PPP2R3B expression was lower in males than in females and was independently correlated with poor clinical outcome. PPP2R3B codes for the PR70 protein, a regulatory substrate-recognizing subunit of protein phosphatase 2A. PR70 decreased melanoma growth by negatively interfering with DNA replication and cell cycle progression through its role in stabilizing the cell division cycle 6 (CDC6)-chromatin licensing and DNA replication factor 1 (CDT1) interaction, which delays the firing of origins of DNA replication. Hence, PR70 functionally behaves as an X-linked tumor suppressor gene.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Redpath, MargaretMcGill Univ, Dept Pathol, Montreal, PQ, Canada.;Lady Davis Inst Med Res, Montreal, PQ, Canada.
(author)
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Elchebly, MounibLady Davis Inst Med Res, Montreal, PQ, Canada.
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Klein, Kathleen OrosLady Davis Inst Med Res, Montreal, PQ, Canada.
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Papadakis, Andreas I.McGill Univ, Dept Pathol, Montreal, PQ, Canada.;Lady Davis Inst Med Res, Montreal, PQ, Canada.
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Wilmott, James S.Royal Prince Alfred Hosp, Melanoma Inst Australia, Sydney, NSW, Australia.;Univ Sydney, Sydney, NSW, Australia.
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Scolyer, Richard A.Royal Prince Alfred Hosp, Melanoma Inst Australia, Sydney, NSW, Australia.;Univ Sydney, Sydney, NSW, Australia.
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Edqvist, Per-HenrikUppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)peedq227
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Pontén, FredrikUppsala universitet,Klinisk och experimentell patologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)fredpont
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Schadendorf, DirkUniv Hosp Essen, Dept Dermatol, Essen, Germany.;German Canc Consortium DKTK, Heidelberg, Germany.
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van Rijk, Anke F.Lady Davis Inst Med Res, Montreal, PQ, Canada.
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Michiels, StefanGustave Roussy, Serv Biostat & Epidemiol, Villejuif, France.;Univ Paris Sud, INSERM, UMR 1018, Ctr Res Epidemiol & Populat Hlth CESP, Le Kremlin Bicetre, France.
(author)
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Dumay, AnneUniv Paris Diderot, Sorbonne Paris Cite, Labex Inflamex, INSERM,UMR S 1149,Ctr Rech Inflammat, Paris, France.
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Helbling-Leclerc, AnneUniv Paris Sud, CNRS, UMR 8200, Villejuif, France.;Univ Paris Sud, Gustave Roussy, CNRS UMR 8200, Villejuif, France.
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Dessen, PhilippeUniv Paris Sud, Gustave Roussy, INSERM UMR 1170, Hematopoiese Normale & Pathol, Villejuif, France.
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Wouters, JasperKatholieke Univ Leuven, Lab Translat Cell & Tissue Res, Leuven, Belgium.;Katholieke Univ Leuven, VIB Ctr Biol Dis, Lab Computat Biol, Leuven, Belgium.;Katholieke Univ Leuven, Dept Human Genet, Leuven, Belgium.
(author)
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Stass, MargueriteKatholieke Univ Leuven, Univ Hosp Leuven, Dept Surg Oncol, Leuven, Belgium.
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Greenwood, Celia M. T.Lady Davis Inst Med Res, Montreal, PQ, Canada.;McGill Univ, Dept Oncol, Montreal, PQ, Canada.;McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada.
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Ghanem, Ghanem E.Univ Libre Bruxelles, Inst Jules Bordet, Lab Oncol & Expt Surg, Brussels, Belgium.
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van den Oord, JoostKatholieke Univ Leuven, Lab Translat Cell & Tissue Res, Leuven, Belgium.
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Feunteun, JeanUniv Paris Sud, Gustave Roussy, CNRS UMR 8200, Villejuif, France.
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Spatz, AlanMcGill Univ, Dept Pathol, Montreal, PQ, Canada.;Lady Davis Inst Med Res, Montreal, PQ, Canada.;McGill Univ, Dept Oncol, Montreal, PQ, Canada.
(author)
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McGill Univ, Dept Pathol, Montreal, PQ, Canada.;Lady Davis Inst Med Res, Montreal, PQ, Canada.Lady Davis Inst Med Res, Montreal, PQ, Canada.
(creator_code:org_t)
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In:Science Translational Medicine: American Association for the Advancement of Science (AAAS)8:3691946-62341946-6242
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van Kempen, Leon ...
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Redpath, Margare ...
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Elchebly, Mounib
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Klein, Kathleen ...
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Papadakis, Andre ...
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Wilmott, James S ...
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Scolyer, Richard ...
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Edqvist, Per-Hen ...
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Pontén, Fredrik
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van Rijk, Anke F ...
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Michiels, Stefan
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Dumay, Anne
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Helbling-Leclerc ...
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Dessen, Philippe
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Wouters, Jasper
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Stass, Marguerit ...
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Greenwood, Celia ...
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Ghanem, Ghanem E ...
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van den Oord, Jo ...
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Feunteun, Jean
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