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PEBP2 alpha B/mouse AML1 consists of multiple isoforms that possess differential transactivation potentials.

机译:PEBP2 alpha B /小鼠AML1由具有不同反式激活潜力的多种同工型组成。

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A murine transcription factor, PEBP2, is composed of two subunits, alpha and beta. There are two genes in the mouse genome, PEBP2 alpha A and PEBP2 alpha B, which encode the alpha subunit. Two types of the alpha B cDNA clones, alpha B1 and alpha B2, were isolated from mouse fibroblasts and characterized. They were found to represent 3.8- and 7.9-kb transcripts, respectively. The 3.8-kb RNA encodes the previously described alpha B protein referred to as alpha B1, while the 7.9-kb RNA encodes a 387-amino-acid protein, termed alpha B2, which is identical to alpha B1 except that it has an internal deletion of 64 amino acid residues. Both alpha B1 and alpha B2 associate with PEBP2 beta and form a heterodimer. The alpha B2/beta complex binds to the PEBP2 binding site two- to threefold more strongly than the alpha B1/beta complex does. alpha B1 stimulates transcription through the PEBP2 site about 40-fold, while alpha B2 is only about 25 to 45% as active as alpha B1. Transactivation domain is located downstream of the 128-amino-acid runt homology region, referred to as the Runt domain. Mouse chromosome mapping studies revealed that alpha A, alpha B, and beta genes are mapped to chromosomes 17, 16, and 8, respectively. The last two genes are syntenic with the human AML1 on chromosome 21q22 and PEBP2 beta/CBF beta on 16q22 detected at the breakpoints of characteristic chromosome translocations of the two different subtypes of acute myeloid leukemia. These results suggest that previously described chimeric gene products, AML1/MTG8(ETO) and AML1-EAP generated by t(8;21) and t(3;21), respectively, lack the transactivation domain of AML1.
机译:鼠转录因子PEBP2由两个亚基α和β组成。小鼠基因组中有两个基因,PEBP2 alpha A和PEBP2 alpha B,它们编码alpha亚基。从小鼠成纤维细胞中分离并鉴定了两种类型的αB cDNA克隆,即αB1和αB2。发现它们分别代表3.8-kb和7.9-kb的转录本。 3.8-kb RNA编码先前描述的称为alpha B1的alpha B蛋白,而7.9-kb RNA编码称为alpha B2的387个氨基酸的蛋白质,该蛋白与alpha B1相同,只是它具有内部缺失64个氨基酸残基。 alpha B1和alpha B2均与PEBP2 beta缔合并形成异二聚体。与BBP /β复合物相比,αB2 /β复合物与PEBP2结合位点的结合强度高2至3倍。 αB1通过PEBP2位点刺激转录约40倍,而αB2的活性只有αB1的25%至45%。反式激活结构域位于128个氨基酸的矮子同源性区域的下游,称为矮子结构域。小鼠染色体作图研究表明,αA,αB和β基因分别被映射到17、16和8号染色体。在急性髓性白血病的两种不同亚型的特征性染色体易位转折点处检测到,后两个基因与21q22号染色体上的人AML1和16q22处的PEBP2 beta / CBF beta具有同义性。这些结果表明,先前描述的嵌合基因产物,分别由t(8; 21)和t(3; 21)生成的AML1 / MTG8(ETO)和AML1-EAP,缺少AML1的反式激活域。

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