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

Vuković, Lidija; Jevtić, Predrag; Zhang, Zhaojie; Stohr, Bradley A.; Levy, Daniel L.

doi:10.1242/jcs.181263

Cited by 43 publications

(70 citation statements)

References 66 publications

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“…In case of importins and exportins, previous work has shown they can be functionally tagged (Miyamoto et al , 2002; Ciciarello et al , 2004; Kimura et al , 2013b; Vuković et al , 2016). This is very well reflected in our data, for example, biotinylated cargos accumulate in the expected cellular compartment over time and known interactors are among the most prominently identified proteins.…”

Section: Discussionmentioning

confidence: 99%

Landscape of nuclear transport receptor cargo specificity

Mackmull

Klaus

Heinze

et al. 2017

Molecular Systems Biology

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Nuclear transport receptors (NTRs) recognize localization signals of cargos to facilitate their passage across the central channel of nuclear pore complexes (NPCs). About 30 different NTRs constitute different transport pathways in humans and bind to a multitude of different cargos. The exact cargo spectrum of the majority of NTRs, their specificity and even the extent to which active nucleocytoplasmic transport contributes to protein localization remains understudied because of the transient nature of these interactions and the wide dynamic range of cargo concentrations. To systematically map cargo–NTR relationships in situ, we used proximity ligation coupled to mass spectrometry (BioID). We systematically fused the engineered biotin ligase BirA* to 16 NTRs. We estimate that a considerable fraction of the human proteome is subject to active nuclear transport. We quantified the specificity and redundancy in NTR interactions and identified transport pathways for cargos. We extended the BioID method by the direct identification of biotinylation sites. This approach enabled us to identify interaction interfaces and to discriminate direct versus piggyback transport mechanisms. Data are available via ProteomeXchange with identifier PXD007976.

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Section: Discussionmentioning

confidence: 99%

Landscape of nuclear transport receptor cargo specificity

Mackmull

Klaus

Heinze

et al. 2017

Molecular Systems Biology

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“…We previously reported that RGP primary melanoma cells exhibit larger nuclei compared to normal melanocytes. We also found that the levels of Nuclear Transport Factor 2 (NTF2) inversely correlate with nuclear size, with decreasing NTF2 levels in melanoma progression correlating with increased nuclear size (Vukovic et al, 2016).…”

Section: Introductionmentioning

confidence: 72%

Nuclear Transport Factor 2 (NTF2) suppresses metastatic melanoma by modifying cell migration, metastasis, and gene expression

Vuković

White

Gigley

et al. 2020

Preprint

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While changes in nuclear structure and organization are frequently observed in cancer cells, relatively little is known about how nuclear architecture impacts cancer progression and pathology. To begin to address this question, we studied Nuclear Transport Factor 2 (NTF2) because its levels decrease during melanoma progression.We show that increasing NTF2 expression in metastatic melanoma cells reduces cell proliferation and motility while increasing apoptosis. We also demonstrate that increasing NTF2 expression in these cells significantly inhibits metastasis and increases survival of mice. Mechanistically, we show that NTF2 levels affect the expression and nuclear positioning of a number of genes associated with cell proliferation and migration. We propose that by decreasing nuclear size and/or lamin A nuclear localization, ectopic expression of NTF2 in metastatic melanoma alters chromatin organization to generate a gene expression profile with characteristics of primary melanoma, concomitantly abrogating several phenotypes associated with advanced stage cancer both in vitro and in vivo. Thus NTF2 acts as a melanoma tumor suppressor to maintain proper nuclear structure and gene expression and could be a novel therapeutic target to improve health outcomes of melanoma patients.

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“…[42][43][44] The size of the nucleus is similarly much larger in X. laevis than X. tropicalis, and is sequentially reduced further during embryonic cleavage stages, enabling the use of these species for investigations of nuclear scaling. The size of the nucleus has been found to also be regulated by Importin α, as well as NTF2, 45,46 and Lamin components. 47,48 Nuclear envelope composition is particularly interesting in Xenopus, as it contributes to regulatory events such as the mid-blastula transition 49 as well as nuclear morphological features such as nuclear branching.…”

Section: Unique Opportunities For Comparative Cell Biologymentioning

confidence: 99%

Advancing genetic and genomic technologies deepen the pool for discovery in Xenopus tropicalis

Kakebeen

Wills

2019

Developmental Dynamics

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Xenopus laevis and Xenopus tropicalis have long been used to drive discovery in developmental, cell, and molecular biology. These dual frog species boast experimental strengths for embryology including large egg sizes that develop externally, well‐defined fate maps, and cell‐intrinsic sources of nutrients that allow explanted tissues to grow in culture. Development of the Xenopus cell extract system has been used to study cell cycle and DNA replication. Xenopus tadpole tail and limb regeneration have provided fundamental insights into the underlying mechanisms of this processes, and the loss of regenerative competency in adults adds a complexity to the system that can be more directly compared to humans. Moreover, Xenopus genetics and especially disease‐causing mutations are highly conserved with humans, making them a tractable system to model human disease. In the last several years, genome editing, expanding genomic resources, and intersectional approaches leveraging the distinct characteristics of each species have generated new frontiers in cell biology. While Xenopus have enduringly represented a leading embryological model, new technologies are generating exciting diversity in the range of discoveries being made in areas from genomics and proteomics to regenerative biology, neurobiology, cell scaling, and human disease modeling.

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

Cited by 43 publications

References 66 publications

Landscape of nuclear transport receptor cargo specificity

Landscape of nuclear transport receptor cargo specificity

Nuclear Transport Factor 2 (NTF2) suppresses metastatic melanoma by modifying cell migration, metastasis, and gene expression

Advancing genetic and genomic technologies deepen the pool for discovery in Xenopus tropicalis

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