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首页> 外文期刊>Molecular and Cellular Biology >Subcellular localization of the alpha and beta subunits of the acute myeloid leukemia-linked transcription factor PEBP2/CBF.
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Subcellular localization of the alpha and beta subunits of the acute myeloid leukemia-linked transcription factor PEBP2/CBF.

机译：急性髓细胞白血病相关转录因子PEBP2 / CBF的α和β亚基的亚细胞定位。

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Each of the two human genes encoding the alpha and beta subunits of a heterodimeric transcription factor, PEBP2, has been found at the breakpoints of two characteristic chromosome translocations associated with acute myeloid leukemia, suggesting that they are candidate proto-oncogenes. Polyclonal antibodies against the alpha and beta subunits of PEBP2 were raised in rabbits and hamsters. Immunofluorescence labeling of NIH 3T3 cells transfected with PEBP2 alpha and -beta cDNAs revealed that the full-size alpha A1 and alpha B1 proteins, the products of two related but distinct genes, are located in the nucleus, while the beta subunit is localized to the cytoplasm. Deletion analysis demonstrated that there are two regions in alpha A1 responsible for nuclear accumulation of the protein: one mapped in the region between amino acids 221 and 513, and the other mapped in the Runt domain (amino acids 94 to 221) harboring the DNA-binding and the heterodimerizing activities. When the full-size alpha A1 and beta proteins are coexpressed in a single cell, the former is present in the nucleus and the latter still remains in the cytoplasm. However, the N- or C-terminally truncated alpha A1 proteins devoid of the region upstream or downstream of the Runt domain colocalized with the beta protein in the nucleus. In these cases, the beta protein appeared to be translocated into the nucleus passively by binding to alpha A1. The chimeric protein containing the beta protein at the N-terminal region generated as a result of the inversion of chromosome 16 colocalized with alpha A1 to the nucleus more readily than the normal beta protein. The implications of these results in relation to leukemogenesis are discussed.
机译：已在与急性髓性白血病相关的两个特征性染色体易位的转折点发现了编码异二聚体转录因子PEBP2的α和β亚基的两个人类基因中的每一个，这表明它们是候选原癌基因。在兔和仓鼠中产生了针对PEBP2的α和β亚基的多克隆抗体。用PEBP2 alpha和-beta cDNA转染的NIH 3T3细胞的免疫荧光标记显示，两个相关但截然不同的基因产物全尺寸alpha A1和alpha B1蛋白位于细胞核中，而beta亚基则位于细胞质。缺失分析表明，αA1中有两个区域负责蛋白质的核积累：一个区域位于221至513位氨基酸之间，另一个区域位于Runt域（94至221位氨基酸）中，具有DNA-结合和异二聚活性。当全尺寸的αA1和β蛋白在单个细胞中共表达时，前者存在于细胞核中，而后者仍保留在细胞质中。但是，N或C末端截短的AlA1蛋白缺少与核中β蛋白共定位的Runt域上游或下游区域。在这些情况下，β蛋白似乎通过与αA1结合而被动地转移到细胞核中。比起正常的β蛋白，由于与αA1共定位的16号染色体倒置而产生的N端区域含有β蛋白的嵌合蛋白更容易产生。讨论了这些结果与白血病发生有关的含义。

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