The oncogenic potential of Jumonji D2 (JMJD2/KDM4) histone demethylase overexpression.
The Jumonji D2 proteins (JMJD2/KDM4) function to demethylate di- and trimethylated (me2/3) histone 3 lysine 9 (H3K9me2/3) and H3K36me3. Knockout mouse models for Kdm4b and Kdm4d have not resulted in gross abnormalities, while mouse models for Kdm4a and Kdm4c have not been reported. However, the KDM4 subfamily of demethylases are overexpressed in several tumor types. Overexpression of KDM4 proteins alters transcription and chromatin remodeling, driving cellular proliferation, anchorage-independent growth, invasion, and migration. Increased proliferation occurs through KDM4-mediated modification of cell cycle timing, as well as through increased numbers of replication forks. Recent evidence also suggests that KDM4C overexpression contributes to the maintenance of a pluripotent state. Together these data suggest that overexpression of KDM4 proteins induces numerous oncogenic effects.
Cross Cancer Institute and the Department of Experimental Oncology, Faculty of Medicine and Dentistry, University of Alberta, 11560 University Avenue, Edmonton, AB T6G 1Z2, Canada.
Leah C
LC
Young
Michael J
MJ
Hendzel
D000818:Animals; D002453:Cell Cycle; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D042002:Chromatin Assembly and Disassembly; D004331:Drosophila melanogaster / Q000201:enzymology / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D056466:Histone Demethylases / Q000235:genetics* / Q000378:metabolism; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008745:Methylation; D051379:Mice; D008822:Mice, Transgenic; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction
D006657:Histones; D007527:Isoenzymes; D056466:Histone Demethylases; C560307:JMJD2A protein, mouse