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.
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. 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.
^Lahoud MH, Ristevski S, Venter DJ, Jermiin LS, Bertoncello I, Zavarsek S, Hasthorpe S, Drago J, de Kretser D, Hertzog PJ, Kola I (August 2001). "Gene targeting of Desrt, a novel ARID class DNA-binding protein, causes growth retardation and abnormal development of reproductive organs". Genome Research11 (8): 1327–34. doi:10.1101/gr.168801. PMID11483573.
^Zhu L, Hu J, Lin D, Whitson R, Itakura K, Chen Y (August 2001). "Dynamics of the Mrf-2 DNA-binding domain free and in complex with DNA". Biochemistry40 (31): 9142–50. doi:10.1021/bi010476a. PMID11478881.
^Kristensen LH, Nielsen AL, Helgstrand C, Lees M, Cloos P, Kastrup JS, Helin K, Olsen L, Gajhede M (June 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". The FEBS Journal279 (11): 1905–14. doi:10.1111/j.1742-4658.2012.08567.x. PMID22420752.
Lu PJ, Sundquist K, Baeckstrom D, Poulsom R, Hanby A, Meier-Ewert S, Jones T, Mitchell M, Pitha-Rowe P, Freemont P, Taylor-Papadimitriou J (May 1999). "A novel gene (PLU-1) containing highly conserved putative DNA/chromatin binding motifs is specifically up-regulated in breast cancer". The Journal of Biological Chemistry274 (22): 15633–45. doi:10.1074/jbc.274.22.15633. PMID10336460.
Kashuba V, Protopopov A, Podowski R, Gizatullin R, Li J, Klein G, Wahlestedt C, Zabarovsky E (June 2000). "Isolation and chromosomal localization of a new human retinoblastoma binding protein 2 homologue 1a (RBBP2H1A)". European Journal of Human Genetics8 (6): 407–13. doi:10.1038/sj.ejhg.5200474. PMID10878660.
Barrett A, Madsen B, Copier J, Lu PJ, Cooper L, Scibetta AG, Burchell J, Taylor-Papadimitriou J (October 2002). "PLU-1 nuclear protein, which is upregulated in breast cancer, shows restricted expression in normal human adult tissues: a new cancer/testis antigen?". International Journal of Cancer101 (6): 581–8. doi:10.1002/ijc.10644. PMID12237901.
Tan K, Shaw AL, Madsen B, Jensen K, Taylor-Papadimitriou J, Freemont PS (June 2003). "Human PLU-1 Has transcriptional repression properties and interacts with the developmental transcription factors BF-1 and PAX9". The Journal of Biological Chemistry278 (23): 20507–13. doi:10.1074/jbc.M301994200. PMID12657635.
Tzschach A, Lenzner S, Moser B, Reinhardt R, Chelly J, Fryns JP, Kleefstra T, Raynaud M, Turner G, Ropers HH, Kuss A, Jensen LR (April 2006). "Novel JARID1C/SMCX mutations in patients with X-linked mental retardation". Human Mutation27 (4): 389. doi:10.1002/humu.9420. PMID16541399.
Yamane K, Tateishi K, Klose RJ, Fang J, Fabrizio LA, Erdjument-Bromage H, Taylor-Papadimitriou J, Tempst P, Zhang Y (March 2007). "PLU-1 is an H3K4 demethylase involved in transcriptional repression and breast cancer cell proliferation". Molecular Cell25 (6): 801–12. doi:10.1016/j.molcel.2007.03.001. PMID17363312.
Barrett A, Santangelo S, Tan K, Catchpole S, Roberts K, Spencer-Dene B, Hall D, Scibetta A, Burchell J, Verdin E, Freemont P, Taylor-Papadimitriou J (July 2007). "Breast cancer associated transcriptional repressor PLU-1/JARID1B interacts directly with histone deacetylases". International Journal of Cancer121 (2): 265–75. doi:10.1002/ijc.22673. PMID17373667.