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メチル化CpG結合蛋白PCM1による癌抑制遺伝子発現の抑制と腫瘍発生との関連性： 藤田直之, 佐谷秀行, 中尾光善　(熊本大・腫瘍医）

Silencing of the tumor suppressor genes by methylated-CpG binding protein PCM1 and its possible implication in tumorigenesis : Naoyuki FUJITA, Hideyuki SAYA, and Mitsuyoshi NAKAO (Dept. of Tumor Genet. Biol., Kumamoto Univ. Sch. of Med.)

DNA methylation of promoter-associated CpG islands is involved in the inactivation of tumor suppressor genes in cancer. However, the mechanisms underlying aberrant methylation and transcriptional repression remain unclear. In this study, we characterized a human PCM1 protein possessing a methyl-CpG binding domain (MBD) and one to three tandem copies of a cysteine-rich domain, due to alternative splicings, that was observed in DNA methyltransferase. The gene located on chromosome 18q which is frequently altered in certain tumors, and it was expressed in most tissues and cancer cell lines. PCM1 protein was normally present in a granular pattern in the nucleus, while mutated PCM1 lacking a MBD localized to the nucleolus. Bacterially expressed PCM1 protein predominantly bound to DNA fragments containing methylated CpG islands from p16, VHL and E-cadherin genes, and PCM1 repressed their transcription activities both in vitro and in the cell. These findings indicated that methyl-CpG binding proteins such as PCM1 play important roles on methylation-dependent silencing of the tumor-associated genes.