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PDF: Inactivation of a Histone Methyltransferase by Mutations in Human ...

Download 2 times Source: cancerres.aacrjournals.org // Topic: Cancer File Size: 164.16 kb // Total of Page: 5 Page(s) Last download by puspitasarisetiawan Last download on: 10 months ago Share this info: Sample of page (click to enlarge) Short Desciption: mutations also occur in human cancer tissues and cell lines, and all ..... that have been found in human cancers (18). Three such mutations, ... Content Inside: [CANCER RESEARCH 63, 7619 7623, November 15, 2003] Advances in Brief Inactivation of a Histone Methyltransferase by Mutations in Human Cancers Keun-Cheol Kim, Liqing Geng, and Shi Huang Program in Cancer Genetics and Epigenetics, Cancer Research Center, The Burnham Institute, La Jolla, California Abstract Histone methyltransferase (HMT)1 class enzymes that methylate lysine residues of histones or proteins contain a conserved catalytic core termed the SET domain, which shares sequence homology with an independently described sequence motif, the PR domain. Intact PR or SET sequence is required for tumor suppression functions, but it remains unclear whether it is histone methyltransferase activity that underlies tumor suppression. We now show that tumor suppressor RIZ1 (PRDM2) methylates histone H3 on lysine 9, and this activity is reduced by mutations in the PR domain found in human cancers. Also, S-adenosylhomocysteine or methyl donor deficiency inhibits RIZ1 and other H3 lysine 9 methylation activities. These results support the hypothesis that H3 lysine 9