Mechanistic and functional extrapolation of SET and MYND domain-containing protein 2 to pancreatic cancer

Figure 2 A schematic model for SET and MYND domain-containing protein 2 driving pancreatic cancer development via methylation of nonhistone proteins. SET and MYND domain-containing protein 2 (SMYD2) can methylate several nonhistone proteins that may be involved in pancreatic cancer tumorigenesis, including p53, PTEN, retinoblastomaassociated protein (RB), and mitogen-activated protein kinase activated protein kinase 3 (MAPKAPK3). SMYD2 methylates and inactivates p53 to promote cell proliferation. PTEN is downregulated by SMYD2-mediated methylation, which promotes cell proliferation through activation of PI3K signaling. Methylation of RB by SMYD2 enhances RB phosphorylation, which allows E2F to disassociate from the RB-E2F complex and enhances E2F activity to promote cell cycle progression. SMYD2 impacts the RTK/Ras pathway through methylation of MAPKAPK3 to promote cell growth. MAPKAPK3: Mitogen-activated protein kinase activated protein kinase 3; RB: Retinoblastoma-associated protein.