Multiple biological processes may be associated with tumorigenesis under NUP88‐overexpressed condition

Li, Jiafeng; Zhao, Jing; Li, Yue

doi:10.1002/gcc.22417

Cited by 9 publications

(10 citation statements)

References 25 publications

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“…In addition, elevated Nup88 expression in a mouse model induces multinuclei by promoting the premitotic destruction of Polo-like kinase 1 (Plk1), a kinase required for bipolar spindle formation and chromosome segregation [ 17 , 18 ]. However, the molecular basis of how Nup88 leads to a multinucleated phenotype is poorly understood because of a lack of information concerning its interacting partners [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

The role of vimentin in the tumor marker Nup88-dependent multinucleated phenotype

2018

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BackgroundNucleoporin Nup88, a component of nuclear pore complexes, is known to be overexpressed in several types of tumor tissue. The overexpression of Nup88 has been reported to promote the early step of tumorigenesis by inducing multinuclei in both HeLa cells and a mouse model. However, the molecular basis of how Nup88 leads to a multinucleated phenotype remains unclear because of a lack of information concerning its binding partners. In this study, we characterize a novel interaction between Nup88 and vimentin. We also examine the involvement of vimentin in the Nup88-dependent multinucleated phenotype.MethodsCells overexpressing tagged versions of Nup88, vimentin and their truncations were used in this study. Coprecipitation and GST-pulldown assays were carried out to analyze protein-protein interactions. Vimentin knockdown by siRNA was performed to examine the functional role of the Nup88-vimentin interaction in cells. The phosphorylation status of vimentin was analyzed by immunoblotting using an antibody specific for its phosphorylation site.ResultsVimentin was identified as a Nup88 interacting partner, although it did not bind to other nucleoporins, such as Nup50, Nup214, and Nup358, in HeLa cell lysates. The N-terminal 541 amino acid residues of Nup88 was found to be responsible for its interaction with vimentin. Recombinant GST-tagged Nup88 bound to recombinant vimentin in a GST-pulldown assay. Although overexpression of Nup88 in HeLa cells was observed mainly at the nuclear rim and in the cytoplasm, colocalization with vimentin was only partially detected at or around the nuclear rim. Disruption of the Nup88-vimentin interaction by vimentin specific siRNA transfection suppressed the Nup88-dependent multinucleated phenotype. An excess amount of Nup88 in cell lysates inhibited the dephosphorylation of a serine residue (Ser83) within the vimentin N-terminal region even in the absence and presence of an exogenous phosphatase. The N-terminal 96 amino acid residues of vimentin interacted with both full-length and the N-terminal 541 residues of Nup88.ConclusionsNup88 can affect the phosphorylation status of vimentin, which may contribute to the Nup88-dependent multinucleated phenotype through changing the organization of vimentin.

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Section: Introductionmentioning

confidence: 99%

The role of vimentin in the tumor marker Nup88-dependent multinucleated phenotype

2018

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“…The alpha-helical domain of Nup62 (Nup62-C1) assists in its centrosome localization (25). We asked how the localization of Nup88 and Nup62 changes during different cell-cycle phases.…”

Section: Nup88 and Nup62 Interaction Is Cell Cycle Independentmentioning

confidence: 99%

“…Nup62 overexpression is reported from the prostate, and ovarian cancers 22,23 , and ROCK1 dependent Nup62 phosphorylation induces p63 nuclear localization and cell proliferation 24 . Multiple physiological roles attributed to Nup88 25 do not provide a clear picture, and the availability of limited information about the Nup88 and Nup62 expression level changes in head and neck cancer 11,24 impedes our understanding of the process. Since Nup88 and Nup62 form stable complex and their expression levels show alterations in different cancers, we have probed how the expression and interactions of Nup88 and Nup62 correlate with head and neck cancers, common cancer in India.…”

Section: Introductionmentioning

confidence: 99%

Overexpressed Nup88 stabilized through interaction with Nup62 promotes NFκB dependent pathways in cancer

Singh

Samaiya

Mishra

2020

Preprint

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Nuclear pores control nucleo-cytoplasmic trafficking and directly or indirectly regulate vital cellular processes. Nup88, important for Crm1 mediated nuclear export process, is overexpressed in many cancers. A positive correlation exists between progressive stages of cancer and Nup88 expression. However, links between Nup88 overexpression and head and neck cancer are insignificant, and mechanistic details are non-existent. Here, we report that Nup88 exhibits positive correlation in head and neck cancer in addition to elevated Nup62 levels. We demonstrate that Nup88 interacts with Nup62 in a cell-cycle and glycosylation independent manner. The overexpression of Nup88 or Nup62 imparts proliferation and migration advantages to cells. We further report that the interaction with Nup62 stabilizes Nup88 by inhibiting proteasome-mediated degradation of overexpressed Nup88. Overexpressed Nup88 is stabile and partly inside the nucleus and can interact with NFB (p65). Nup88 overexpression induces proliferative and inflammatory responses downstream of p65. Altogether, we suggest that simultaneous overexpression of Nup62 and Nup88 in head and neck cancer stabilizes overexpressed Nup88. Stable Nup88 interacts with p65 and induces inflammatory, proliferative, and migratory advantages to cells, which perhaps is the underlying mechanism driving tumorigenic transformations.

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“…The overexpressed nucleoporin is found in aggregates in the cytoplasm and higher expression correlates with cancer progression and poor prognosis [138,139]. A recent study has mapped the interactome of Nup88 and demonstrated that the nucleoporin blocks Misp spindle localization that is critical for normal spindle formation and chromosome separation [140]. …”

Section: Npcs In the Development And Progression Of Cancersmentioning

confidence: 99%

The roles of the nuclear pore complex in cellular dysfunction, aging and disease

Sakuma

D’Angelo

2017

Seminars in Cell & Developmental Biology

110

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The study of the Nuclear Pore Complex (NPC), the proteins that compose it (nucleoporins), and the nucleocytoplasmic transport that it controls has revealed an unexpected layer to pathogenic disease onset and progression. Recent advances in the study of the regulation of NPC composition and function suggest that the precise control of this structure is necessary to prevent diseases from arising or progressing. Here we discuss the role of nucleoporins in a diverse set of diseases, many of which directly or indirectly increase in occurrence and severity as we age, and often shorten the human lifespan. NPC biology has been shown to play a direct role in these diseases and therefore in the process of healthy aging.

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Multiple biological processes may be associated with tumorigenesis under NUP88‐overexpressed condition

Cited by 9 publications

References 25 publications

The role of vimentin in the tumor marker Nup88-dependent multinucleated phenotype

The role of vimentin in the tumor marker Nup88-dependent multinucleated phenotype

Overexpressed Nup88 stabilized through interaction with Nup62 promotes NFκB dependent pathways in cancer

The roles of the nuclear pore complex in cellular dysfunction, aging and disease

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