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白血病に関与するキメラタンパク質AML1-MTG8によるAML1/PEBP2の核マトリックスの解離：陳琳峰、村上洋太、伊藤嘉明（京大・ウイルス研・がんウイルス）

Displacement of AML1/PEBP2aB1 from the nuclear matrix by leukemogenic AML1-MTG8: Lin-Feng CHEN, Yota MURAKAMI, Yoshiaki ITO (Dept. of Viral Oncol., Inst. Virus Res., Kyoto Univ.)

AML1/PEBP2aB1 plays important roles in hematopoiesis and leukemogenesis and is associated with the nuclear matrix. In addition to transactivation function, AML1/PEBP2αB1 was found to stimulate polyomavirus (Py) DNA replication through its cognate binding site. We analyzed the relationship between the nuclear matrix binding and the stimulation of Py DNA replication since the nuclear matrix is believed to play important roles in DNA replication in eukaryotic cells. We have shown previously that the replication activation domain (RAD) is localized to a.a. 302-371 and RAD itself contains the nuclear matrix targeting activity. The chimeric protein AML1-MTG8(ETO) does not have sequence homologous to RAD. However, we found that AML1-MTG8 also bound to the nuclear matrix and competed with AML1 for the nuclear matrix association. As increasing amounts of AML1-MTG8 was expressed, AML1 was gradually displaced from the nuclear matrix. AML1-MTG8 inhibited Py DNA replication stimulated by AML1 specifically and the inhibition was proportional to the degree of loss of AML1 from nuclear matrix. These results suggest that nuclear matrix association is required for AML1 to stimulated Py DNA replication and that AML1-MTG8 inhibits the activity of AML1 by competing for nuclear matrix association. RAD is largely overlapping with the transcription activation domain, and since nuclear matrix is also thought to be important for transcriptional regulation, it is possible that inhibition of the nuclear matrix binding of AML1 by AML1-ETO may affect the transcription activity of AML1/PEBP2αB1.