How do you reduce EZH2?
Inhibitors of EZH2 methyltransferase activity. The first EZH2 inhibitor was 3-deazaneplanocin A (DZNep). DZNep, a known S-adenosyl-L-homocysteine (SAH) hydrolase inhibitor, indirectly inhibits EZH2 through the increase of SAH, which directly represses S-adenosyl-L-methionine-dependent histone methyltransferase activity …
What is the function of EZH2?
The EZH2 gene provides instructions for making a type of enzyme called a histone methyltransferase. Histone methyltransferases modify proteins called histones, which are structural proteins that attach (bind) to DNA and give chromosomes their shape.
How do EZH2 inhibitors work?
It works by binding in the cofactor binding pocket of DNA methyltransferases to block methyl transfer. EI1 is another inhibitor, developed by Novartis, that showed EZH2 inhibitory activity in lymphoma tumor cells, including cells with the Y641 mutation.
What is gene overexpression in cancer?
In biology, to make too many copies of a protein or other substance. Overexpression of certain proteins or other substances may play a role in cancer development.
What causes EZH2 mutation?
It is caused by heterozygous mutations in enhancer of zeste homolog 2 (EZH2), a histone methyltransferase responsible for histone H3 at lysine 27 (H3K27) trimethylation.
What’s the function of EZH2 in terms of chromatin dynamics?
Biological function of EZH2. PRC2 is an essential chromatin modifier that is conserved across organisms from plants to flies and humans3. This complex represses the transcription of target genes through trimethylation of lysine 27 on histone 3 (H3K27me3), which is currently viewed as its predominant function in vivo4.
Is EZH2 a tumor suppressor?
EZH2 downregulates expression of tumor suppressor genes and upregulates oncogenes, promoting cancer cell survival, proliferation, epithelial to mesenchymal and invasion. In particular, EZH2 has been also reported to be associated with drug resistance to chemotherapy and targeted therapy.
How does gene overexpression work?
The most common mechanism is likely via post-translational modifications. (J) Overexpression can activate new pathways via neomorphic effects. Here, overexpression of the normally cytoplasmic protein A results in accumulation of a subpopulation in the nucleus, which causes a novel phenotype.
What causes gene overexpression?
Gene Expression Gene overexpression or downregulation can be due to processes such as gene amplification, activating mutation, or epigenetic activation.