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首页> 美国卫生研究院文献>Proceedings of the National Academy of Sciences of the United States of America >The human programmed cell death-2 (PDCD2) gene is a target of BCL6 repression: Implications for a role of BCL6 in the down-regulation of apoptosis
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The human programmed cell death-2 (PDCD2) gene is a target of BCL6 repression: Implications for a role of BCL6 in the down-regulation of apoptosis

机译：人类程序性细胞死亡2（PDCD2）基因是BCL6抑制的目标：对BCL6在下调细胞凋亡中的作用的暗示

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BCL6, a gene on chromosome 3 band q27, encodes a Kruppel-type zinc finger transcriptional repressor. Rearrangements of this gene are frequent in various kinds of lymphomas, particularly of the large-cell B-cell type. The BCL6 nuclear phosphoprotein is expressed in a variety of tissues and is up-regulated particularly in lymph node germinal centers. The zinc fingers of BCL6 bind DNA in a sequence-specific manner. To identify targets of the BCL6 repressive effects, we used a VP16-BCL6 fusion protein containing the zinc fingers but devoid of the repressor domains to compete with the binding of endogenous BCL6 in a transiently transfected B-cell line and then performed subtractive hybridization by using a method to selectively amplify sequences that are differentially expressed. We found that the programmed cell death-2 (PDCD2) gene is a target of BCL6 repression. This gene is the human homolog of Rp8, a rat gene associated with programmed cell death in thymocytes. Immunohistochemistry reveals the anticipated inverse relationship between BCL6 and PDCD2 expression in human tonsil. PDCD2 is detectable in cells of the germinal center in areas where there is less BCL6 expression as well as in the mantle zone, where there is little or no BCL6 expression. These results raise the possibility that BCL6 may regulate apoptosis by means of its repressive effects on PDCD2. BCL6 deregulation may lead to persistent down-regulation of PDCD2, reduced apoptosis, and, as a consequence, accumulation of BCL6-containing lymphoma cells.
机译：BCL6是3号染色体q27染色体上的一个基因，编码Kruppel型锌指转录阻遏物。该基因的重排在各种类型的淋巴瘤中尤其是大细胞B细胞类型中很常见。 BCL6核磷蛋白在多种组织中表达，尤其在淋巴结生发中心上调。 BCL6的锌指以序列特异性方式结合DNA。为了确定BCL6阻遏作用的靶标，我们使用了一个VP16-BCL6融合蛋白，该蛋白含有锌指但没有阻遏物域，以与瞬时转染的B细胞系中内源性BCL6的结合竞争，然后通过使用一种选择性扩增差异表达序列的方法。我们发现程序性细胞死亡2（PDCD2）基因是BCL6压制的目标。该基因是Rp8的人类同源物，Rp8是与胸腺细胞中程序性细胞死亡相关的大鼠基因。免疫组织化学揭示了人类扁桃体中BCL6和PDCD2表达之间预期的逆向关系。在BCL6表达较少的区域以及BCL6表达很少或没有的地幔区域的生发中心细胞中可检测到PDCD2。这些结果提高了BCL6可能通过其对PDCD2的抑制作用来调节细胞凋亡的可能性。 BCL6的失调可能导致PDCD2的持续下调，凋亡减少，并因此导致含BCL6的淋巴瘤细胞积聚。

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