Lysine-specific demethylase 5B also known as histone demethylase JARID1B is a demethylase enzyme that in humans is encoded by the KDM5B gene.[1][2][3]
Interactions
JARID1B has been shown to interact with FOXG1[4] and PAX9.[4]
Role
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. [5] 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. [6] 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. [7] Further research needs to be done to determine Jarid1B function in cancer development and its function as a histone demethylase.
References
- ^ Lahoud MH, Ristevski S, Venter DJ, Jermiin LS, Bertoncello I, Zavarsek S, Hasthorpe S, Drago J, de Kretser D, Hertzog PJ, Kola I (Aug 2001). "Gene targeting of Desrt, a novel ARID class DNA-binding protein, causes growth retardation and abnormal development of reproductive organs". Genome Res 11 (8): 1327–34. doi:10.1101/gr.168801. PMID 11483573.
- ^ Zhu L, Hu J, Lin D, Whitson R, Itakura K, Chen Y (Jul 2001). "Dynamics of the Mrf-2 DNA-binding domain free and in complex with DNA". Biochemistry 40 (31): 9142–50. doi:10.1021/bi010476a. PMID 11478881.
- ^ "Entrez Gene: JARID1B jumonji, AT rich interactive domain 1B".
- ^ a b Tan, Keith; Shaw Anthony L, Madsen Bente, Jensen Kirsten, Taylor-Papadimitriou Joyce, Freemont Paul S (Jun 2003). "Human PLU-1 Has transcriptional repression properties and interacts with the developmental transcription factors BF-1 and PAX9". J. Biol. Chem. (United States) 278 (23): 20507–13. doi:10.1074/jbc.M301994200. ISSN 0021-9258. PMID 12657635.
- ^ 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
- ^ 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
- ^ 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 reading
- Lu PJ, Sundquist K, Baeckstrom D et al. (1999). "A novel gene (PLU-1) containing highly conserved putative DNA/chromatin binding motifs is specifically up-regulated in breast cancer.". J. Biol. Chem. 274 (22): 15633–45. doi:10.1074/jbc.274.22.15633. PMID 10336460.
- Kashuba V, Protopopov A, Podowski R et al. (2000). "Isolation and chromosomal localization of a new human retinoblastoma binding protein 2 homologue 1a (RBBP2H1A).". Eur. J. Hum. Genet. 8 (6): 407–13. doi:10.1038/sj.ejhg.5200474. PMID 10878660.
- Barrett A, Madsen B, Copier J et al. (2002). "PLU-1 nuclear protein, which is upregulated in breast cancer, shows restricted expression in normal human adult tissues: a new cancer/testis antigen?". Int. J. Cancer 101 (6): 581–8. doi:10.1002/ijc.10644. PMID 12237901.
- Tan K, Shaw AL, Madsen B et al. (2003). "Human PLU-1 Has transcriptional repression properties and interacts with the developmental transcription factors BF-1 and PAX9.". J. Biol. Chem. 278 (23): 20507–13. doi:10.1074/jbc.M301994200. PMID 12657635.
- Ota T, Suzuki Y, Nishikawa T et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
- Patsialou A, Wilsker D, Moran E (2005). "DNA-binding properties of ARID family proteins". Nucleic Acids Res. 33 (1): 66–80. doi:10.1093/nar/gki145. PMC 546134. PMID 15640446.
- Tzschach A, Lenzner S, Moser B et al. (2006). "Novel JARID1C/SMCX mutations in patients with X-linked mental retardation". Hum. Mutat. 27 (4): 389. doi:10.1002/humu.9420. PMID 16541399.
- Yamane K, Tateishi K, Klose RJ et al. (2007). "PLU-1 is an H3K4 demethylase involved in transcriptional repression and breast cancer cell proliferation". Mol. Cell 25 (6): 801–12. doi:10.1016/j.molcel.2007.03.001. PMID 17363312.
- Barrett A, Santangelo S, Tan K et al. (2007). "Breast cancer associated transcriptional repressor PLU-1/JARID1B interacts directly with histone deacetylases". Int. J. Cancer 121 (2): 265–75. doi:10.1002/ijc.22673. PMID 17373667.
External links
- JARID1B protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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