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PEBP2 (AML1)、C/EBPa、PU.1による協調的転写活性化と白血病関連遺伝子産物AML1-MTG8による転写抑制の分子機構の解析: 菅野智彦,菅野由香,金優栄,伊藤嘉明
（京大・ウイルス研）

Multiple transactivation elements of PEBP2 are differentially utilized to synergize with C/EBP alpha and PU.1, and AML1-MTG8 selectively inhibits C/EBP alpha-dependent transcription: Tomohiko KANNO, Yuka KANNO, Woo-Young KIM, Yoshiaki ITO (Inst. Virus Research, Kyoto Univ.)

The polyomavirus enhancer binding protein-2 (PEBP2) is a key factor for establishing definitive hematopoiesis and is also associated with chromosomal abnormalities in leukemia. PEBP2 strongly activates transcription only when it collaborates with other transcription factors. Here we examined synergistic transactivation involving PEBP2, PU.1, and C/EBP alpha. A major transactivation element of the PEBP2 alpha subunit (TE1) was required for synergy with PU.1, whereas a distinct less potent transactivation element, (TE3), was required for synergism with C/EBP alpha. In the latter case, the transactivation elements of C/EBP alpha that directly interacted with the basal transcription machinery cooperated with PEBP2. No evidence for cooperative DNA binding between PEBP2, C/EBP alpha and PU.1 was evident. These results suggest that PEBP2 forms intermolecular transactivating modules with partners to enhance basal transcription machinery recruitment, and that it does so in different conformations depending on its interacting partners.
A leukemogenic fusion protein derived from the PEBP2 alpha subunit, AML1/ETO (AML1-MTG8), directly inhibited C/EBP alpha-mediated transactivation, but did not inhibit those with PU.1 and PEBP2. Our results suggest that AML1/ETO selectively interferes with normal PEBP2 function by targeting select partner proteins and changes the spectrum of PEBP2-mediated synergistic transactivation.