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首页> 外文期刊>Carcinogenesis >Complex relationship between TCTP, microtubules and actin microfilaments regulates cell shape in normal and cancer cells.
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Complex relationship between TCTP, microtubules and actin microfilaments regulates cell shape in normal and cancer cells.

机译:TCTP,微管和肌动蛋白微丝之间的复杂关系调节正常和癌细胞的细胞形状。

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Translationally controlled tumor-associated protein (TCTP) is a ubiquitous and highly conserved protein implicated in cancers. Here, we demonstrate that interactions of TCTP with microtubules (MTs) are functionally important but indirect, and we reveal novel interaction of TCTP with the actin cytoskeleton. Firstly, immunofluorescence in Xenopus XL2 cells revealed cytoplasmic fibers stained with TCTP but not with tubulin antibodies, as well as MTs free of TCTP. Furthermore, TCTP localized to a subset of actin-rich fibers in migrating cells. Secondly, Xenopus laevis TCTP did not affect in vitro assembly/disassembly of MTs and lacked MT-binding affinity both in pull-down assays and in cell-free extracts. Although TCTP also failed to bind to purified filamentous actin (F-actin), it was associated with microfilaments in cell-free extracts. Thirdly, TCTP concentrated in mitotic spindle did not colocalize with MTs and was easily dissociated from these structures except at the poles. Finally, RNA interference knockdown of TCTP in XL2 and HeLa cells provoked drastic, MT-dependent shape change. These data show that although TCTP interacts with MTs, it does not behave as classic MT-associated protein. Our evidence for an association of TCTP with F-actin structures, and for an involvement in cell shape regulation, implicates this protein in integrating cytoskeletal interactions both in interphase and mitosis providing a new avenue to fully understand the role of TCTP.
机译:翻译控制的肿瘤相关蛋白(TCTP)是一种普遍存在且高度保守的蛋白,与癌症有关。在这里,我们证明了TCTP与微管(MTs)的相互作用在功能上很重要,但却是间接的,并且我们揭示了TCTP与肌动蛋白细胞骨架的新颖相互作用。首先,非洲爪蟾XL2细胞的免疫荧光显示胞质纤维被TCTP染色,但未被微管蛋白抗体染色,而MTs不含TCTP。此外,TCTP位于迁移细胞中富含肌动蛋白的纤维的子集。其次,非洲爪蟾TCTP不会影响MT的体外组装/拆卸,并且在下拉试验和无细胞提取物中均缺乏MT结合亲和力。尽管TCTP也无法结合纯化的丝状肌动蛋白(F-肌动蛋白),但它与无细胞提取物中的微丝有关。第三,TCTP集中在有丝分裂纺锤体中不与MTs共定位,除了极点外,很容易从这些结构上解离。最终,XL2和HeLa细胞中TCTP的RNA干扰敲低引发了剧烈的,MT依赖性的形状变化。这些数据表明,尽管TCTP与MT相互作用,但它的行为不像经典的MT相关蛋白。我们的证据表明TCTP与F-肌动蛋白的结构有关,并且参与细胞形状的调节,提示该蛋白参与整合了相间和有丝分裂的细胞骨架相互作用,为全面了解TCTP的作用提供了新途径。

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