title: Loss of the retinoblastoma binding protein 2 (RBP2) histone demethylase suppresses tumorigenesis in mice lacking Rb1 or Men1.
abstract: Aberrations in epigenetic processes, such as histone methylation, can cause cancer. Retinoblastoma binding protein 2 (RBP2; also called JARID1A or KDM5A) can demethylate tri- and dimethylated lysine 4 in histone H3, which are epigenetic marks for transcriptionally active chromatin, whereas the multiple endocrine neoplasia type 1 (MEN1) tumor suppressor promotes H3K4 methylation. Previous studies suggested that inhibition of RBP2 contributed to tumor suppression by the retinoblastoma protein (pRB). Here, we show that genetic ablation of Rbp2 decreases tumor formation and prolongs survival in Rb1(+/-) mice and Men1-defective mice. These studies link RBP2 histone demethylase activity to tumorigenesis and nominate RBP2 as a potential target for cancer therapy.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Wenchu
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authors.forename: Mike R
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authors.lastname: Minamishima
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authors.lastname: Zhang
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authors.lastname: Kulkarni
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authors.lastname: Signoretti
authors.forename: Scott J
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authors.lastname: Rodig
authors.forename: Roderick T
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authors.lastname: Bronson
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authors.lastname: Orkin
authors.forename: David P
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authors.lastname: Tuck
authors.forename: Elizaveta V
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authors.lastname: Benevolenskaya
authors.forename: Matthew
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authors.lastname: Meyerson
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authors.lastname: Kaelin
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mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D057890:Epigenomics; D056466:Histone Demethylases; D006657:Histones / Q000378:metabolism; D008745:Methylation; D051379:Mice; D018345:Mice, Knockout; D009369:Neoplasms / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D011518:Proto-Oncogene Proteins / Q000172:deficiency*; D016160:Retinoblastoma Protein / Q000172:deficiency*; D054840:Retinol-Binding Proteins, Cellular / Q000037:antagonists & inhibitors / Q000172:deficiency*; D015996:Survival Rate
chemical_list: D004791:Enzyme Inhibitors; D006657:Histones; C484898:Men1 protein, mouse; D011518:Proto-Oncogene Proteins; C518460:Rbp2 protein, mouse; D016160:Retinoblastoma Protein; D054840:Retinol-Binding Proteins, Cellular; D056466:Histone Demethylases