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AML1/PEBP2aB1/Cbfa2 の DNA 結合における分子内制御機構とβサブユニットおよび Ets-1 による調節：
金優榮,伊藤嘉明（京大 ・ウイルス 研・癌ウイルス）

Intramolecular negative regulation of AML1/PEBP2aB/Cbfa2 and its modulation by the b subunit and Ets-1 : Woo-Young KIM and Yoshiaki ITO (Department of Viral Oncology, Institute for Virus Research, Kyoto University)

AML1/PEBP2aB/CBFa2 plays pivotal roles in development of hematopoietic cells and leukemogenesis. The product of this gene represents an a subunit of PEBP2/CBF and , together with b sunbunit, function as a unique transcription factor: it displays only a weak transcription stimulation by itself but it cooperates with other transcription factors such as Ets-1. Each of PEBP2aB and Ets-1 by its own bind to DNA poorly. The DNA binding domain of Ets-1, the Ets domain, is masked by the auto-inhibitory domain encoded by exon VII located at the N-terminal side of the Ets domain. We found that the DNA binding domain of PEBP2aB, the Runt domain, was also masked by the region termed the negative regulatory domain for DNA binding (NRDB) intramolecularly. When b subunit is heterodimerized with a subunit, it interacts the Runt domain. This interaction is blocked by the C-terminal end of a subunit. When b subunit is allowed to interact with the Runt domain, the DNA binding activity of the Runt domain is releaved from NRDB and the heterodimer binds to DNA stably. When PEBP2aB and Ets-1 were mixed, a dramatic increase of the DNA binding of each of the two protein was observed in the absence of b subunit. This cooperative DNA binding can be observed only when both PEBP2 and Ets-1 binding sites were intact. By deletion analysis, we found that NRDB of PEBP2aB directly interacts with the exon VII region of Ets-1 and the direct interaction of the auto-inhibitory domains of the two proteins was found to cancel the negative effect of each of the negative regulatory domains. When PEBP2aB and Ets-1 bound to DNA, b subunit bound to the complex and stabilized the complex on DNA.