title: Nuclear size is sensitive to NTF2 protein levels in a manner dependent on Ran binding.
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.
authors.affiliation: Department of Molecular Biology, University of Wyoming, Laramie, WY 82071, USA.
authors.forename: Lidija D
authors.initials: LD
authors.lastname: Vuković
authors.affiliation: Department of Molecular Biology, University of Wyoming, Laramie, WY 82071, USA.
authors.forename: Predrag
authors.initials: P
authors.lastname: Jevtić
authors.affiliation: Department of Zoology and Physiology, University of Wyoming, Laramie, WY 82071, USA.
authors.forename: Zhaojie
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Pathology, University of California, San Francisco, CA 94143, USA.
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Stohr
authors.affiliation: Department of Molecular Biology, University of Wyoming, Laramie, WY 82071, USA dlevy1@uwyo.edu.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Levy
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D002467:Cell Nucleus / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D053145:Cell Nucleus Size; D006801:Humans; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics / Q000378:metabolism*; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D014982:Xenopus laevis; D020931:ran GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: C038965:NUTF2 protein, human; D029543:Nucleocytoplasmic Transport Proteins; D011257:Pregnancy Proteins; D020931:ran GTP-Binding Protein
keywords: Cancer; Development; Melanoma; NTF2; Nuclear pore complex; Nuclear scaling; Nuclear size; Nuclear structure; Nuclear transport; Nucleus; Ran; Xenopus
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