title: The Role of Nuclear Receptor-Binding SET Domain Family Histone Lysine Methyltransferases in Cancer.
abstract: The nuclear receptor-binding SET Domain (NSD) family of histone H3 lysine 36 methyltransferases is comprised of NSD1, NSD2 (MMSET/WHSC1), and NSD3 (WHSC1L1). These enzymes recognize and catalyze methylation of histone lysine marks to regulate chromatin integrity and gene expression. The growing number of reports demonstrating that alterations or translocations of these genes fundamentally affect cell growth and differentiation leading to developmental defects illustrates the importance of this family. In addition, overexpression, gain of function somatic mutations, and translocations of NSDs are associated with human cancer and can trigger cellular transformation in model systems. Here we review the functions of NSD family members and the accumulating evidence that these proteins play key roles in tumorigenesis. Because epigenetic therapy is an important emerging anticancer strategy, understanding the function of NSD family members may lead to the development of novel therapies.
authors.affiliation: Departments of Medicine, Biochemistry and Molecular Biology and University of Florida Health Cancer Center, The University of Florida, Gainesville, Florida 32610.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Bennett
authors.affiliation: Departments of Medicine, Biochemistry and Molecular Biology and University of Florida Health Cancer Center, The University of Florida, Gainesville, Florida 32610.
authors.forename: Alok
authors.initials: A
authors.lastname: Swaroop
authors.affiliation: Departments of Medicine, Biochemistry and Molecular Biology and University of Florida Health Cancer Center, The University of Florida, Gainesville, Florida 32610.
authors.forename: Catalina
authors.initials: C
authors.lastname: Troche
authors.affiliation: Departments of Medicine, Biochemistry and Molecular Biology and University of Florida Health Cancer Center, The University of Florida, Gainesville, Florida 32610.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Licht
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic; D015870:Gene Expression; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D051379:Mice; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D000074463:PR-SET Domains; D011499:Protein Processing, Post-Translational; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins
chemical_list: D006657:Histones; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; D011495:Histone-Lysine N-Methyltransferase; C419586:NSD2 protein, human