Nuclear size is sensitive to NTF2 protein levels in a manner dependent on Ran binding

Journal of Cell Science
Lidija D VukovićDaniel L Levy

Abstract

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.

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Citations

Jan 13, 2018·Cold Spring Harbor Protocols·Pan Chen, Daniel L Levy
Nov 1, 2018·Molecular Biology of the Cell·Alison D WaltersOrna Cohen-Fix
May 31, 2019·Current Genetics·Helena Cantwell, Paul Nurse
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Oct 23, 2019·The Journal of Cell Biology·Pan ChenDaniel L Levy
Feb 1, 2020·Wiley Interdisciplinary Reviews. Developmental Biology·Chase C WesleyDaniel L Levy
Oct 18, 2018·Molecular Biology of the Cell·Matthew R DilsaverDaniel L Levy
Jul 1, 2020·Annual Review of Cell and Developmental Biology·Wallace F Marshall
Mar 30, 2021·Current Genetics·Pallavi DeolalKrishnaveni Mishra
May 31, 2020·Developmental Cell·Richik Nilay MukherjeeDaniel L Levy

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