Nucleolar localization of the nucleophosmin-anaplastic lymphoma kinase is not required for malignant transformation.
Nucleolar localization of the nucleophosmin-anaplastic lymphoma kinase is not required for malignant transformation.
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发表时间：
1998-03
期刊：
影响因子：
11.2
通讯作者：
D. Mason;K. Pulford;D. Bischof;M. U. Kuefer;L. H. Butler;L. Lamant;G. Delsol;S. Morris
中科院分区：
文献类型：
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作者：
D. Mason;K. Pulford;D. Bischof;M. U. Kuefer;L. H. Butler;L. Lamant;G. Delsol;S. Morris
（2）; 5）（p23; q35）淋巴瘤相关染色体易位产生了一种新的融合基因，该基因整合了间变性淋巴瘤激酶（ALK）受体酪氨酸激酶和核磷蛋白基因的部分。我们在这里报告，该融合基因的产物在肿瘤细胞的核仁内积累，并且以前的报告主要是蛋白质的细胞质定位代表了组织加工工件。然而，核仁磷蛋白-ALK的核仁蓄积可能不是其致癌作用所必需的，因为携带变异体（1;2）染色体易位的淋巴瘤中表达的ALK蛋白不在核仁中蓄积。此外，工程化的杂合TPR-ALK蛋白可以转化啮齿动物成纤维细胞并在小鼠中产生淋巴瘤，同时保持局限于细胞质。我们认为ALK的转化作用可能不依赖于其核仁定位，这一假设可能对研究融合基因产生后重新定位的其他参与肿瘤发生的蛋白质具有影响。
The (2;5)(p23;q35) lymphoma-associated chromosomal translocation creates a novel fusion gene that incorporates parts of the anaplastic lymphoma kinase (ALK) receptor tyrosine kinase and nucleophosmin genes. We report here that the product of this fusion gene accumulates within the nucleoli of neoplastic cells, and that previous reports of a predominantly cytoplasmic localization for the protein represent a tissue-processing artifact. However, nucleolar accumulation of nucleophosmin-ALK may not be necessary for its oncogenic action, because an ALK protein expressed in a lymphoma carrying a variant (1;2) chromosomal translocation did not accumulate in nucleoli. Furthermore, an engineered hybrid TPR-ALK protein can transform rodent fibroblasts and produce lymphomas in mice while remaining confined to the cytoplasm. We propose that the transforming action of ALK may not be reliant on its nucleolar localization, a hypothesis that may have implications for studies of other proteins involved in oncogenesis that are relocalized after the creation of fusion genes.