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JARID1B
Lysine-specific demethylase 5B also known as histone demethylase JARID1B is a demethylase enzyme that in humans is encoded by the ''KDM5B'' gene.〔(【引用サイトリンク】 url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10765 )〕
== Function ==
Jarid1B (also known as KDM5B or PLU1) is in the family of JHDM genes. These are responsible for demethylation of tri- and di-methylated lysines in the 4 position of histone 3 (H3K4me3 and H3K4me2). Jarid1B is a multidomain enzyme that is part of the subfamily KDM5. The whole Jarid1 family is a protein family that possesses H3K4 histone demethylase activity.〔Kristensen, L. H., Nielsen, A. L., Helgstrand, C., Lees, M., Cloos, P., Kastrup, J. S., . . . Gajhede, M. (2012). Studies of H3K4me3 demethylation by KDM5B/Jarid1B/PLU1 reveals strong substrate recognition in vitro and identifies 2,4-pyridine-dicarboxylic acid as an in vitro and in cell inhibitor. FEBS J, 279(11), 1905-1914. doi: 10.1111/j.1742-4658.2012.08567.x〕 The biological roles JHDM genes have been shown to potentially playing a role in cancer. Jarid1B has been implicated in the development of prostate, breast, and skin cancer and also has been associated with melanoma maintenance. Knockout mice (Jarid1b−/−) produced are viable in neonatal life. These mice do exhibit the phenotype of premature mortality, decreased fertility in female mice, reduction in body weight and impairment in mammary gland development. It also acted to decrease serum estrogen levels and caused reduced mammary epithelial cell proliferation in the early stages of puberty. These Jarid1b−/− mice seem to be greatly affected in many regulators of the development of mammy development such as FOXA1 and estrogen receptor α.〔Zou, M. R., Cao, J., Liu, Z., Huh, S. J., Polyak, K., & Yan, Q. (2014). Histone demethylase jumonji AT-rich interactive domain 1B (JARID1B) controls mammary gland development by regulating key developmental and lineage specification genes. J Biol Chem, 289(25), 17620-17633. doi: 10.1074/jbc.M114.570853〕 However, others have shown that a Jarid1B knockout embryos usually have neonatal lethality due to the failure of their respiratory system. Knockout embryos have also been seen to have several different neural defects including: disorganized cranial nerves, increased incidences of exencephaly, and defects in eye development.〔Albert, M., Schmitz, S. U., Kooistra, S. M., Malatesta, M., Morales Torres, C., Rekling, J. C., . . . Helin, K. (2013). The histone demethylase Jarid1b ensures faithful mouse development by protecting developmental genes from aberrant H3K4me3. PLoS Genet, 9(4), e1003461. doi: 10.1371/journal.pgen.1003461〕 Further research needs to be done to determine Jarid1B function in cancer development and its function as a histone demethylase.
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