Vuković Lidija D, Jevtić Predrag, Zhang Zhaojie, Stohr Bradley A, Levy Daniel L
Department of Molecular Biology, University of Wyoming, Laramie, WY 82071, USA.
Department of Zoology and Physiology, University of Wyoming, Laramie, WY 82071, USA.
J Cell Sci. 2016 Mar 15;129(6):1115-27. doi: 10.1242/jcs.181263. Epub 2016 Jan 28.
Altered nuclear size is associated with many cancers, and determining whether cancer-associated changes in nuclear size contribute to carcinogenesis necessitates an understanding of mechanisms of nuclear size regulation. Although nuclear import rates generally positively correlate with nuclear size, NTF2 levels negatively affect nuclear size, despite the role of NTF2 (also known as NUTF2) in nuclear recycling of the import factor Ran. We show that binding of Ran to NTF2 is required for NTF2 to inhibit nuclear expansion and import of large cargo molecules in Xenopus laevis egg and embryo extracts, consistent with our observation that NTF2 reduces the diameter of the nuclear pore complex (NPC) in a Ran-binding-dependent manner. Furthermore, we demonstrate that ectopic NTF2 expression in Xenopus embryos and mammalian tissue culture cells alters nuclear size. Finally, we show that increases in nuclear size during melanoma progression correlate with reduced NTF2 expression, and increasing NTF2 levels in melanoma cells is sufficient to reduce nuclear size. These results show a conserved capacity for NTF2 to impact on nuclear size, and we propose that NTF2 might be a new cancer biomarker.
核大小改变与多种癌症相关，要确定癌症相关的核大小变化是否有助于致癌作用，就需要了解核大小调控机制。尽管核输入速率通常与核大小呈正相关，但NTF2水平会对核大小产生负面影响，尽管NTF2（也称为NUTF2）在输入因子Ran的核循环中发挥作用。我们发现，在非洲爪蟾卵和胚胎提取物中，Ran与NTF2的结合是NTF2抑制核扩张和大货物分子输入所必需的，这与我们观察到的NTF2以Ran结合依赖的方式减小核孔复合体（NPC）直径一致。此外，我们证明在非洲爪蟾胚胎和哺乳动物组织培养细胞中异位表达NTF2会改变核大小。最后，我们表明黑色素瘤进展过程中核大小的增加与NTF2表达降低相关，而在黑色素瘤细胞中增加NTF2水平足以减小核大小。这些结果表明NTF2具有影响核大小的保守能力，我们提出NTF2可能是一种新的癌症生物标志物。
