The SET and MYND domain-containing protein 3 (SMYD3) gene was found to encode a novel histone methyltransferase involved in human cancer cells. It could specifically methylate histone H3 at lysine 4 and activate the transcription of a set of downstream genes, including of several oncogenes (e.g., N-Myc, CrkL, Wnt10b, RIZ, and hTERT) and genes involved in the control of cell cycle (e.g., Cyclin G1 and CDK2) and signal transduction (e.g., STAT1, MAP3K11, and PIK3CB). To determine the effects of SMYD3 overexpression on cell transformation, serum dependence and apoptosis sensitivity, we expressed SMYD3 in NIH3T3 cells, and these cells showed several transformed phenotypes as demonstrated by foci formation and colony growth in soft agar. Besides, these transfectants also showed increased serum dependence and depression of sensitivity to apoptosis induced by dexamethasone. These findings lend further understanding to the role of SMYD3 in the genesis of human cancers and might throw light on the development of novel therapeutic approaches to human cancers.
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