Phospho-Ezh2 (Thr311) Antibody #27888

The polycomb group (PcG) proteins are involved in maintaining the silenced state of several developmentally regulated genes and contribute to the maintenance of cell identity, cell cycle regulation, and oncogenesis (1,2). Enhancer of zeste homolog 2 (Ezh2), a member of this large protein family, contains four conserved regions including domain I, domain II, and a cysteine-rich amino acid stretch that precedes the carboxy-terminal SET domain (3). The SET domain has been linked with histone methyltransferase (HMTase) activity. Moreover, mammalian Ezh2 is a member of a histone deacetylase complex that functions in gene silencing, acting at the level of chromatin structure (4). Ezh2 complexes methylate histone H3 at Lys9 and 27 in vitro, which is thought to be involved in targeting transcriptional regulators to specific loci (5). Ezh2 is deregulated in various tumor types, and its role, both as a primary effector and as a mediator of tumorigenesis, has become a subject of increased interest (6).
Ezh2 is phosphorylated on Thr311 by AMP-activated protein kinase (AMPK) in response to sustained energy starvation (7). Phosphorylation of Thr311 disrupts the interaction between Ezh2 and SUZ12, leading to attenuation of Ezh2 histone methyltransferase activity and suppression of oncogenic function (7). In addition, phosphorylation of Ezh2 on Thr311 correlates with better survival in ovarian and breast cancer patients (7).