Thursday, June 12, 2014
Stanford University and GlaxoSmithKline plc researchers have
uncovered the mechanism of action of SMYD3, a histone lysine methyltransferase
overexpressed in many lung and pancreatic tumors.1 The surprise was
that SMYD3 acts in the cytoplasm to regulate the MAPK pathway and not in the nucleus as previously thought. The discovery
implies that inhibiting the enzyme can counter activating mutations in MAPK
pathway components such as K-Ras.
part of an ongoing collaboration to characterize the function of epigenetic
targets, the Stanford-GSK team started by analyzing gene expression data for 54
histone lysine methyltransferases in a panel of pancreatic cancers with high
SMYD3 thus appears to be a good target for a subset of
KRAS-driven tumors. "If you have cancers driven by KRAS and have high
levels of SMYD3 or methylation of MAP3K2, these are good candidates for SMYD3
inhibition," said Gozani.
L. SciBX 7(23);
Published online June 12, 2014
1. Mazur, P.K. et al.
Nature; published online May 21, 2014; doi:10.1038/nature13320
Contact: Julien Sage, Stanford University School of Medicine, Stanford,
Contact: Or Gozani, Stanford University, Stanford, Calif.
2. Cain, C. SciBX 7(19);
(NASDAQ:EPZM), Cambridge, Mass.
GlaxoSmithKline plc (LSE:GSK; NYSE:GSK), London, U.K.
Stanford University, Stanford, Calif.
Stanford University School of Medicine, Stanford, Calif.