Epigenetic Functions of SMYD5 and Its Role in Development, Cancer and Other Cellular Processes

The lysine methyltransferase SMYD5 is an important regulator of development and has been implicated in multiple malignancies, such as heart disease, lung and gastric cancers, breast and hepatocellular carcinomas, and inflammatory bowel disease. Further, SMYD5 has been linked to the mild hypothermia response, RNA translation, and HIV-1 transcription. SMYD5 is ubiquitously expressed in lymphocytes and the fetal brain, retina, heart, gut, liver, and reproductive organs. Mechanistically, SMYD5 methylates histone residues H3K36, H3K37, and H4K20, as well as non-histone targets such as the ribosomal protein RPL40 and the HIV-1 Tat protein. Here, we review the literature on SMYD5, focusing on its epigenetic functions and its roles in development, cancer, and other biological processes.