The multifunctional FUS, EWS and TAF15 proto-oncoproteins show cell type-specific expression patterns and involvement in cell spreading and stress response.
The multifunctional FUS, EWS and TAF15 proto-oncoproteins show cell type-specific expression patterns and involvement in cell spreading and stress response.
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DOI：
10.1186/1471-2121-9-37
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发表时间：
2008-07-11
期刊：
影响因子：
--
通讯作者：
Aman P
中科院分区：
文献类型：
--
作者：
Andersson MK;Ståhlberg A;Arvidsson Y;Olofsson A;Semb H;Stenman G;Nilsson O;Aman P
FUS，EWS和TAF15是结构上相似的多功能蛋白，在人类肉瘤和白血病中融合癌基因的表征最初发现。该蛋白质属于RNA结合蛋白的FET（以前是TET）家族，与中央细胞过程有关，例如基因表达的调节，基因组完整性的维持和mRNA/microRNA处理。在本研究中，我们研究了FET蛋白在多种人体组织和细胞类型中的表达和细胞定位。
FUS，EWS和TAF15在人体组织中以不同的和重叠的模式表达。这三种蛋白显示出几乎普遍存在的核表达，FUS和TAF15在大多数细胞类型的细胞质中加上加上。很少检测到细胞质EWS，主要是在分泌细胞类型中看到的。此外，在分化的人类胚胎干细胞，在诱导神经母细胞瘤细胞分化的过程中，在末端分化的黑素细胞和心脏肌肉细胞中不存在FET表达。将FET蛋白靶向是由热休克和氧化应激诱导的胁迫颗粒，而FUS则需要其RNA结合结构域才能进行这种易位。此外，在粘附细胞的扩散起始中心中检测到FUS和TAF15。
我们的结果表明，FET蛋白的细胞特异性表达模式和功能，而不是从早期研究推断出的管家角色。 FET蛋白在胁迫颗粒上的定位表明在压力条件下翻译调节中的活性。在压力反应，翻译控制和粘附等中心过程中的作用可能解释了FET蛋白经常参与人类癌症。
FUS, EWS and TAF15 are structurally similar multifunctional proteins that were first discovered upon characterization of fusion oncogenes in human sarcomas and leukemias. The proteins belong to the FET (previously TET) family of RNA-binding proteins and are implicated in central cellular processes such as regulation of gene expression, maintenance of genomic integrity and mRNA/microRNA processing. In the present study, we investigated the expression and cellular localization of FET proteins in multiple human tissues and cell types. FUS, EWS and TAF15 were expressed in both distinct and overlapping patterns in human tissues. The three proteins showed almost ubiquitous nuclear expression and FUS and TAF15 were in addition present in the cytoplasm of most cell types. Cytoplasmic EWS was more rarely detected and seen mainly in secretory cell types. Furthermore, FET expression was downregulated in differentiating human embryonic stem cells, during induced differentiation of neuroblastoma cells and absent in terminally differentiated melanocytes and cardiac muscle cells. The FET proteins were targeted to stress granules induced by heat shock and oxidative stress and FUS required its RNA-binding domain for this translocation. Furthermore, FUS and TAF15 were detected in spreading initiation centers of adhering cells. Our results point to cell-specific expression patterns and functions of the FET proteins rather than the housekeeping roles inferred from earlier studies. The localization of FET proteins to stress granules suggests activities in translational regulation during stress conditions. Roles in central processes such as stress response, translational control and adhesion may explain the FET proteins frequent involvement in human cancer.
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影响因子：
64.5
作者：
de Hoog, CL;Foster, LJ;Mann, M
通讯作者：
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