Structural assembly of Polycomb group protein and Insight of EZH2 in cancer progression: A review.

Abstract

Polycomb group proteins (PcG) are multi-subunit structure, consisting of polycomb repressive complex 1 (PRC1), PRC2/3, and pleiohomeotic repressive complex. PRC1 is made up of PHC, BMI-1, CBX, and Ring 1A/B. PRC2 protein complex included embryonic ectoderm development, PCL, SUZ12, SET domain, enhancer of zeste homolog-2 protein (EZH2), and Nurf55. The third subunit PhoRC consists of Pho and DSFMBT subunits. One of the important subunits of PcG group of protein is EZH2 (a histone methyltransferase), which catalyzes tri-methylation of histone H3 at Lys 27 (H3K27me3) to regulate gene expression through epigenetic machinery and induces silencing of specific gene transcription. In case of breast cancer and prostate cancer, EZH2 is very well studied. Evidence shows that EZH2 is overexpressed and mutated in a variety of human cancers, rendering EZH2 an attractive target for the design of new chemotherapeutic drugs in cancer. EZH2 also functions both as a transcriptional suppressor and a transcriptional co-activator, depending on H3K27me3 or its absence. In this review, we summarized various studies reported till date, elucidating the structure of PRC2 complex, various mechanisms involved with this, and highlighting the role of EZH2 in breast cancer and prostate cancer progression. An increased understanding of the mechanisms that underlie the pathogenesis of wide spectrum of cancers is therefore needed to develop novel therapeutic approaches for this disease and to improve the quality of life in patients.