Figure 1. SMYD3 in cancer. Mazur et al. have identified the role of SET and MYND domain containing 3 (SMYD3) in K-Ras (KRAS)-driven lung and pancreatic cancers.

In certain lung and pancreatic tumors, activating mutations in KRAS or BRAF (a) lead to excessive signaling through downstream MAPK signaling pathways. One branch of the pathway utilizes mitogen-activated protein kinase kinase kinase 2 (MAP3K2) (b) to activate downstream effectors mitogen-activated protein kinase kinase 5 (MAP2K5; MEK5) and MAP kinase 7 (MAPK7; BMK1;
ERK-5) (c), which drive tumor growth (d).

The team uncovered that the histone lysine methyltransferase SMYD3 can methylate (CH3) MAP3K2 (e), leaving the kinase stuck in an active state to promote hyperactive proliferative signaling.