An open and shut case for the role of NSD proteins as oncogenes

The three components of the mammalian nuclear SET domain containing protein (NSD) family have been implicated in multiple diseases and cancers, but very little is known about their mechanisms of action. NSD proteins are epigenetic regulators and methylate lysine side chains, particularly lysine 36 of histone H3 (H3K36), where they appear to deposit mono and/or dimethyl marks. This modification (H3K36Me) has been shown to be important in various processes including gene expression, alternative splicing and DNA repair. Here, we examine recent findings regarding the oncogenic role of NSD proteins and suggest that a de-regulated switch between H3K36Me and H3K27Me plays an important role in the oncogenic potential of NSD proteins.