Thursday, June 12, 2014
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
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;
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.