Lysine-specific demethylase 5B

Definition:

Histone demethylase that demethylates 'Lys-4' of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-9' or H3 'Lys-27'. Demethylates trimethylated, dimethylated and monomethylated H3 'Lys-4'. Acts as a transcriptional corepressor for FOXG1B and PAX9. Favors the proliferation of breast cancer cells by repressing tumor suppressor genes such as BRCA1 and HOXA5. In contrast, may act as a tumor suppressor for melanoma. Represses the CLOCK-BMAL1 heterodimer-mediated transcriptional activation of the core clock component PER2 (By similarity).

References:

[1]. Catrine Johansson, et al. Structural analysis of human KDM5B guides histone demethylase inhibitor development. Nat Chem Biol. 2016 Jul;12(7):539-45. [Content Brief]

[2]. Jesper Christensen, et al. RBP2 belongs to a family of demethylases, specific for tri-and dimethylated lysine 4 on histone 3. Cell. 2007 Mar 23;128(6):1063-76. [Content Brief]

[3]. Yan Zhang, et al. The PHD1 finger of KDM5B recognizes unmodified H3K4 during the demethylation of histone H3K4me2/3 by KDM5B. Protein Cell. 2014 Nov;5(11):837-50. [Content Brief]

[4]. Kenichi Yamane, et al. PLU-1 is an H3K4 demethylase involved in transcriptional repression and breast cancer cell proliferation. Mol Cell. 2007 Mar 23;25(6):801-12. [Content Brief]

[5]. John R Horton, et al. Characterization of a Linked Jumonji Domain of the KDM5/JARID1 Family of Histone H3 Lysine 4 Demethylases. J Biol Chem. 2016 Feb 5;291(6):2631-46. [Content Brief]

[6]. Keith Tan, et al. Human PLU-1 Has transcriptional repression properties and interacts with the developmental transcription factors BF-1 and PAX9. J Biol Chem. 2003 Jun 6;278(23):20507-13. [Content Brief]

[7]. Alexander Roesch, et al. Re-expression of the retinoblastoma-binding protein 2-homolog 1 reveals tumor-suppressive functions in highly metastatic melanoma cells. J Invest Dermatol. 2006 Aug;126(8):1850-9. [Content Brief]

[8]. Anthony Tumber, et al. Potent and Selective KDM5 Inhibitor Stops Cellular Demethylation of H3K4me3 at Transcription Start Sites and Proliferation of MM1S Myeloma Cells. Cell Chem Biol. 2017 Mar 16;24(3):371-380. [Content Brief]

[9]. Vassilios Bavetsias, et al. 8-Substituted Pyrido[3,4-d]pyrimidin-4(3H)-one Derivatives As Potent, Cell Permeable, KDM4 (JMJD2) and KDM5 (JARID1) Histone Lysine Demethylase Inhibitors. J Med Chem. 2016 Feb 25;59(4):1388-409. [Content Brief]

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