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EZH 2: an emerging role in melanoma biology and strategies for targeted therapy
Author(s) -
Tiffen Jessamy,
Gallagher Stuart J.,
Hersey Peter
Publication year - 2015
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12280
Subject(s) - ezh2 , histone methyltransferase , epigenetics , biology , histone , histone methylation , chromatin , cancer research , histone h3 , melanoma , cancer epigenetics , gene silencing , chromatin remodeling , genetics , gene , dna methylation , gene expression
Summary Histone modifications are increasingly being recognized as important epigenetic mechanisms that govern chromatin structure and gene expression. EZH 2 is the catalytic subunit of the polycomb repressive complex 2 ( PRC 2), responsible for tri‐methylation of lysine 27 on histone 3 (H3K27me3) that leads to gene silencing. This highly conserved histone methyltransferase is found to be overexpressed in many different types of cancers including melanoma, where it is postulated to abnormally repress tumor suppressor genes. Somatic mutations have been identified in approximately 3% of melanomas, and activating mutations described within the catalytic SET domain of EZH 2 confer its oncogenic activity. In the following review, we discuss the evidence that EZH 2 is an important driver of melanoma progression and we summarize the progress of EZH 2 inhibitors against this promising therapeutic target.