Post-translational modifications of EZH2 in cancer
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Cell & Bioscience Open Access
REVIEW
Post‑translational modifications of EZH2 in cancer Zhongwei Li1,2† , Minle Li1,2†, Diandian Wang1†, Pingfu Hou1,2, Xintian Chen1, Sufang Chu1, Dafei Chai1,2, Junnian Zheng1,2* and Jin Bai1,2*
Abstract Enhancer of zeste homolog 2 (EZH2), as a main component of Polycomb Repressive Complex 2, catalyzes histone H3K27me3 to silence its target gene expression. EZH2 upregulation results in cancer development and poor prognosis of cancer patients. Post-translational modifications (PTMs) are important biological events in cancer progression. PTMs regulate protein conformation and diversity functions. Recently, mounting studies have demonstrated that EZH2 stability, histone methyltransferase activity, localization, and binding partners can be regulated by PTMs, including phosphorylation, O-GlcNAcylation, acetylation, methylation and ubiquitination. However, the detailed molecular mechanisms of the EZH2-PTMs and whether other types of PTMs occur in EZH2 remain largely unclear. This review presents an overview of different roles of EZH2 modification and EZH2-PTMs crosstalk during tumorigenesis and cancer metastasis. We also discussed the therapeutic potential of targeting EZH2 modifications for cancer therapy. Keywords: EZH2, Post-translational modification, Crosstalk, Cancer therapy Introduction Dynamic regulation of histone modifications has a critical role in the modulation of gene expression [1]. Recent studies on cancer progression have observed aberrant expression of chromatin regulators that modify histones [2–7]. Previous studies have demonstrated the correlation between the chromatin modifier Enhancer of Zeste Homolog 2 (EZH2) and cancer tumorigenesis and metastasis [8–10]. EZH2, a key histone methyltransferase (HMTase), is the enzymatic subunit of Polycomb Repressive Complex 2 (PRC2), which catalyzes the trimethylation of lysine 27 of histone H3 (H3K27me3) leading to transcriptional silencing [11–14]. Since its discovery in 1996 [15, 16], only now has EZH2 been thought as an
*Correspondence: [email protected]; [email protected] † Zhongwei Li, Minle Li and Diandian Wang contributed equally to this work 1 Cancer Institute, Xuzhou Medical University, 84 West Huaihai Road, Xuzhou 221002, Jiangsu Province, China Full list of author information is available at the end of the article
important histone methyltransferase in cancer progression [4, 17]. EZH2 reportedly promotes cancer development and metastasis [9, 17, 18]. EZH2 can regulate many cellular processes, such as migration, cell cycle, proliferation, DNA repair, apoptosis, and senescence, to facilitate cell survival or promote the malignant transformation of cells [8, 19–27]. For instance, EZH2 can promote the invasion and metastasis by suppressing E-cadherin transcriptional expression [28, 29]; EZH2 can also increase tumorigenesis by silencing tumor suppressors [9, 20, 25]. The functional regulation of EZH2 is important because of its several crucial roles in cancer progression. Many types of mechanisms regulate EZH2 func
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