Aberrant intracellular localization of SET‐CAN fusion protein, associated with a leukemia, disorganizes nuclear export
Aberrant intracellular localization of SET‐CAN fusion protein, associated with a leukemia, disorganizes nuclear export
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DOI：
10.1002/ijc.20296
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发表时间：
2004-09
影响因子：
6.4
通讯作者：
Shoko Saito;Mary Miyaji-Yamaguchi;K. Nagata
中科院分区：
文献类型：
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作者：
Shoko Saito;Mary Miyaji-Yamaguchi;K. Nagata
SET-CAN 融合基因是在 9q34 上发现的与急性未分化白血病相关的染色体重排的产物。 SET-CAN 编码几乎完整的 SET 蛋白，与 CAN 的 C 端三分之二融合。 SET 也称为 TAF-Iβ，是一种组蛋白伴侣和蛋白磷酸酶 2A 的细胞内抑制剂，而 CAN 与核孔蛋白 Nup214 相同。为了深入了解 SET/TAF-Iβ-CAN/Nup214 的致白血病功能，我们检查了其亚细胞定位。免疫荧光分析表明，SET/TAF-Iβ 和 CAN/Nup214 分别存在于细胞核和核膜中，而大多数 SET/TAF-Iβ-CAN/Nup214 位于细胞核中。 SET/TAF-Iβ-CAN/Nup214 与核输出因子之一 hCRM1 相互作用，并导致 hCRM1 的异常细胞内定位。在表达 SET/TAF-Iβ-CAN/Nup214 的细胞中，一种含有核输出信号的蛋白质在细胞核中积累。 hCRM1 的过度表达部分恢复了该蛋白的输出。这些结果表明与 SET/TAF-Iβ-CAN/Nup214 相关的异常定位分子可能参与肿瘤发生。 © 2004 Wiley-Liss, Inc.
The SET‐CAN fusion gene is the product of a chromosomal rearrangement found on 9q34 associated with an acute undifferentiated leukemia. SET‐CAN encodes an almost complete SET protein fused to the C‐terminal two‐thirds of CAN. SET is also known as TAF‐Iβ, a histone chaperone and intracellular inhibitor of protein phosphatase 2A, whereas CAN is identical to Nup214, a nucleoporin protein. To obtain insight into the leukemogenic function of SET/TAF‐Iβ‐CAN/Nup214, we have examined its subcellular localization. Immunofluorescence analyses showed that SET/TAF‐Iβ and CAN/Nup214 are found in the nucleus and the nuclear envelope, respectively, whereas the majority of SET/TAF‐Iβ‐CAN/Nup214 is localized in the nucleus. SET/TAF‐Iβ‐CAN/Nup214 interacted with hCRM1, one of the nuclear export factors, and caused aberrant intracellular localization of hCRM1. In cells expressing SET/TAF‐Iβ‐CAN/Nup214, a protein containing a nuclear export signal accumulated in the nucleus. The export of this protein was partially restored by overexpression of hCRM1. These results suggest that aberrantly localized molecules associated with SET/TAF‐Iβ‐CAN/Nup214 may be involved in oncogenesis. © 2004 Wiley‐Liss, Inc.