ライフサイエンスコーパス: KDM

1 ed scintillation proximity assay (SPA) for 3 KDMs: KDM1A (LSD1), KDM3A (JMJD1A), and KDM4A (JMJD2A).

2 rts stating that UTY(KDM6C) is inactive as a KDM, we demonstrate by biochemical studies, employing MS

3 hylated peptides are first demethylated by a KDM, and a protein methyltransferase (PMT) is added to m

4 ing MS and NMR, that UTY(KDM6C) is an active KDM.

5 anslational modifications than other KMT and KDMs.

6 scovery and characterization of the KMTs and KDMs and the methyl modifications they regulate.

7 iants causing haploinsufficiency of KMTs and KDMs are frequently encountered in individuals with deve

8 ting animal models, we determine 22 KMTs and KDMs as additional candidates for dominantly inherited d

9 We discuss the localization of the KMTs and KDMs as well as the distribution of lysine methylation t

10 nally, we discuss the regulation of KMTs and KDMs by proteasomal degradation, posttranscriptional mec

11 We show that KMTs and KDMs that are associated with, or are candidates for, do

12 ogical application of inhibitors of PMTs and KDMs with emphasis on key advancements in the field.

13 dicate that recruitment of specific RDMs and KDMs is required for efficient transcriptional derepress

14 s 1-6 are able to simultaneously target both KDM families and have been validated as potential antitu

15 the function of all the known and candidate KDMs in myoblast and osteoblast differentiation using th

16 hat KDM3B, KDM6A, and KDM8 are the candidate KDMs required for osteoblast differentiation.

17 to simultaneously delete Lysine Demethylase (KDM) 5A, 5B and 5C efficiently in vitro and in vivo This

18 n affecting genes of the lysine demethylase (KDM) family.

19 nt JmjC histone N-methyl lysine demethylase (KDM) inhibitors which bind to Fe(II) in the active site.

20 abolism, including TET2, lysine demethylase (KDM) KDM6A, BRCA1-associated BAP1, and citric acid cycle

21 sion through the H3K27-specific demethylase (KDM)6B.

22 transferases (KMT) and histone demethylases (KDM) that mediate histone methylation and repress gene e

23 ferent types of histone lysine demethylases (KDM), LSD1/KDM1 and JMJD2/KDM4, are coexpressed and colo

24 methyltransferases (KMTs) and demethylases (KDMs) underpin gene regulation.

25 The JmjC histone demethylases (KDMs) are linked to tumour cell proliferation and are cu

26 ransferases (PMTs) and histone demethylases (KDMs) play an important role in the regulation of gene e

27 The Jumonji C lysine demethylases (KDMs) are 2-oxoglutarate- and Fe(II)-dependent oxygenase

28 Histone lysine demethylases (KDMs) are epigenetic enzymes that can remove both repres

29 Jumonji C (JmjC) lysine demethylases (KDMs) are Fe(II)-dependent hydroxylases that catalyze th

30 Histone lysine demethylases (KDMs) are of critical importance in the epigenetic regul

31 The lysine demethylases (KDMs) catalyze the demethylation of lysine residues on h

32 transferases (KMTs) and lysine demethylases (KDMs) have been implicated in the differentiation of mes

33 transferases (KMTs) and lysine demethylases (KDMs) that regulate them.

34 geting histone N-methyl-lysine demethylases (KDMs) with small molecules both for the generation of pr

35 imited homology to JmjC lysine demethylases (KDMs).

36 e comparable to that of the flavin-dependent KDM LSD1.

37 bly, the preferred sequence requirements for KDM and RDM activity vary even with the same JmjC enzyme

38 n optimized continuous fluorescent assay for KDMs that detects formaldehyde production during demethy

39 The results expand the set of human KDMs and will be of use in developing selective KDM inhi

40 rification and kinetic analysis of the human KDMs JMJD2A and JMJD2D using these methods yielded activ

41 milies of N-methyl-lysine demethylases (JmjC KDMs, KDM2-7), focusing on the academic and patent liter

42 he 2-oxoglutarate- and oxygen-dependent JmjC KDMs, respectively), proceeds via oxidation of the N-met

43 ing that, in purified form, a subset of JmjC KDMs can also act as RDMs, both on histone and non-histo

44 ogical importance, recombinant forms of JmjC KDMs generally display low enzymatic activity and have r

45 bed here is broadly applicable to other JmjC KDMs, facilitating their biochemical characterization an

46 urification scheme for Strep(II)-tagged JmjC KDMs that minimizes contamination by transition state me

47 The JmjC KDMs are Fe(II) and 2-oxoglutarate (2OG)-dependent oxyge

48 substrate-competitive inhibitors of the JmjC KDMs.

49 We conclude that alterations of KDM family members represent a disease-driving mechanism

50 ys have been developed to find inhibitors of KDMs, most of which are fluorescence-based assays.

51 ur analysis identified that LSD1 is the only KDM required for myogenic differentiation and that KDM3B

52 onal analysis for an entire family of KMT or KDM enzymes has not been performed.

53 s of the KDM4A-C with selectivity over other KDMs/2OG oxygenases, including closely related KDM4D/E i

54 ld selectivity towards KDM2A/7A versus other KDMs, as well as cellular activity at low micromolar con

55 ned and synthesized hybrid LSD1/JmjC or "pan-KDM" inhibitors 1-6 by coupling the skeleton of tranylcy

56 st coupled assays are suitable for screening KDMs in 384-well format (Z' factors of 0.70-0.80), facil

57 s and will be of use in developing selective KDM inhibitors.

58 ginine-methylated and sequences in which the KDM's methylated target lysine is substituted for a meth

59 and structural studies which are relevant to KDM inhibitor development.