What is EZH2 in cancer?
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Abstract. EZH2 is the catalytic subunit of the polycomb repressive complex 2 (PRC2), which is a highly conserved histone methyltransferase that methylates lysine 27 of histone 3. Overexpression of EZH2 has been found in a wide range of cancers, including those of the prostate and breast.
What is the mutation in melanoma?
About 50% of cutaneous melanomas have a mutated or damaged copy of the BRAF (pronounced bee-raf) protein. A BRAF mutation makes the cell divide out of control and resist death, causing cancer. Researchers call this a ‘driver mutation’ because it gives the mutated cell a survival advantage over other cells in the body.
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.
Does EZH2 bind to DNA?
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 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.
What does the EZH2 gene do?
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 EZH2 mutation?
Mutations of this gene have been identified in cancers of blood-forming tissues (lymphomas and leukemias). These mutations are described as “gain-of-function” because they appear to enhance the activity of the EZH2 enzyme or give the enzyme a new, atypical function.
What is the role of EZH2 in cancer?
When mutation or abnormal expression happens, EZH2 is related to cancer initiation, metastasis, immunity, metabolism, and drug resistance As there are many important roles of EZH2 in cancer, therapies targeting EZH2 have been important strategies in treatment of many types of cancer.
What is the pathophysiology of Ezh2 expression in cutaneous melanoma?
EZH2 expression is associated with high proliferation rate and aggressive tumor subgroups in cutaneous melanoma and cancers of the endometrium, prostate, and breast. J Clin Oncol. 2006;24(2):268–273.
What is the pathophysiology of zeste homolog 2 protein (EZH2) mutations?
In cancer, gain-of-function mutations in the gene encoding the enhancer of zeste homolog 2 protein (EZH2) lead to a genome-wide increase in histone-3 Lys27 trimethylation (H3K27me3) associated wi … Chromatin is organized into topologically associating domains (TADs) enriched in distinct histone marks.
Why screen for EZH2 mutations and over-expression?
Screening predictive biomarkers, such as EZH2 mutation or over-expression, to help select patients suitable for EZH2 target therapy is important in personalized, precision therapy.