JAK3-mediated phosphorylation of EZH2: a novel mechanism of non-canonical EZH2 activation and oncogenic function

The enhancer of zeste homologue 2 (EZH2) is the catalytic subunit of polycomb-repressive complex 2 (PRC2) and promotes the trimethylation of the histone H3 lysine 27 (H3K27me3) acting as an epigenetic repressor of gene expression (1). Recent studies have shown that EZH2 is upregulated in various solid and hematologic malignancies and its expression is associated with disease progression and poor prognosis. Numerous studies have demonstrated the presence of EZH2 gain of function mutations in a variety of cancers including B cell lymphomas (2), and activation of upstream oncogenic pathways including RAS, MEK-ERK and Rb-E2F (3) being involved in the activation of EZH2 in cancer cells.