Regulation and role of post-translational modifications of enhancer of zeste homologue 2 in cancer development.

Post-translational modifications (PTMs) are critical molecular events which alter protein conformation after their synthesis and diversity protein properties by modulating their stability, localization, interacting partners or the activity of their substrates, consequently exerting pivotal roles in regulating the functions of many important eukaryotic proteins. It has been well acknowledged that PTMs are of great importance in a broad range of biological processes such as gene regulation, cell proliferation, differentiation and apoptosis, tissue development, diseases, tumor progression and drug resistance. As the core and contributing catalytic subunit of Polycomb repressive complex 2(PRC2), Enhancer of zeste homolog 2 (EZH2) is a master epigenetic regulator, often serving as a highly conserved histone methyltransferase (HMTase) to induce histone H3 lysine 27 trimethylation (H3K27me3) and repress gene transcription and expression. Dysregulated EZH2 expression is frequently associated with cancer development and poor prognosis in a wide variety of cancers. Considered its essential role in carcinogenesis, EZH2 is a potential candidate for cancer targeted therapy. Remarkably, mounting evidence highlights that EZH2 expression, activity and stability can be regulated by PTMs including phosphorylation, acetylation, ubiquitination, sumoylation and GlcNAcylation aside from its well-validated modifications in transcriptional and post-transcriptional levels. However, the precise regulatory mechanisms underlying EZH2 PTMs and whether other types of PTMs orchestrate in EZH2 remain largely unclear. In this review, we summarize current advances in the understanding of EZH2 regulation by PTMs and their associated biological functions during tumorigenesis.