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Review
. 2018 Jan 25;9(76):34429-34448.
doi: 10.18632/oncotarget.24319. eCollection 2018 Sep 28.

Prominent role of histone lysine demethylases in cancer epigenetics and therapy

Avilala Janardhan  1   2 , Chandrasekhar Kathera  2 , Amrutha Darsi  2 , Wajid Ali  2 , Lingfeng He  2 , Yanhua Yang  1 , Libo Luo  1 , Zhigang Guo  2
Affiliations
Review

Prominent role of histone lysine demethylases in cancer epigenetics and therapy

Avilala Janardhan et al. Oncotarget. .

Abstract

Protein methylation has an important role in the regulation of chromatin, gene expression and regulation. The protein methyl transferases are genetically altered in various human cancers. The enzymes that remove histone methylation have led to increased awareness of protein interactions as potential drug targets. Specifically, Lysine Specific Demethylases (LSD) removes methylated histone H3 lysine 4 (H3K4) and H3 lysine 9 (H3K9) through formaldehyde-generating oxidation. It has been reported that LSD1 and its downstream targets are involved in tumor-cell growth and metastasis. Functional studies of LSD1 indicate that it regulates activation and inhibition of gene transcription in the nucleus. Here we made a discussion about the summary of histone lysine demethylase and their functions in various human cancers.

Keywords: epigenetics; histone modifications; lysine specific demethylases; protein methylation; therapeutics.

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Conflict of interest statement

CONFLICTS OF INTEREST There is no conflicts of interest.

Figures

Figure 1
Figure 1. Regulation of transcriptional elongation: LSD2 associated with transcriptional elongation factors and phosphorylated RNA polymerase II
Figure 2
Figure 2. Regulation of p53: LSD1 demethylate lysine 370 of the tumor suppressor p53, repressing its function by interacting with 53BP1
Figure 3
Figure 3. Coactivator function: Androgen and LSD1 colocalize on promoters and stimulate H3K9 demethylation without altering the H3K4 methylation status and promote ligand dependent transcription of AR target genes resulting in enhanced tumor cell growth
Figure 4
Figure 4. Interacting proteins map for LSD1: A group of proteins that interact with LSD1, picture was generated by STRING software
See this image and copyright information in PMC

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