Tumor marker nucleoporin 88kDa regulates nucleocytoplasmic transport of NF-κB

Takahashi, Nozomi; Kilsdonk, Jeroen W.J. van; Ostendorf, Benedikt; Smeets, Ruben; Bruggeman, Sophia W.M.; Alonso, Ángel; Loo, Faj van de; Schneider, Matthias; Berg, Wim B. van den; Swart, Guido W.M.

doi:10.1016/j.bbrc.2008.06.128

Cited by 41 publications

(32 citation statements)

References 28 publications

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“…The lethality phenotype of null mos7 mutations agrees with its potential function in general NES-mediated nuclear export. Partial lossof-function mutations in Drosophila mbo or depletion of mammalian Nup88 lead to increased nuclear export, resulting in reduced retention of Drosophila Rel protein Dorsal and NF-kB, respectively (Uv et al, 2000;Xylourgidis et al, 2006;Takahashi et al, 2008). Our analysis suggests that nuclear accumulation of snc1, NPR1, and EDS1 is controlled in part by MOS7.…”

Section: Discussionmentioning

confidence: 72%

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Nuclear Pore Complex Component MOS7/Nup88 Is Required for Innate Immunity and Nuclear Accumulation of Defense Regulators inArabidopsis

et al. 2009

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Plant immune responses depend on dynamic signaling events across the nuclear envelope through nuclear pores. Nuclear accumulation of certain resistance (R) proteins and downstream signal transducers are critical for their functions, but it is not understood how these processes are controlled. Here, we report the identification, cloning, and analysis of Arabidopsis thaliana modifier of snc1,7 (mos7-1), a partial loss-of-function mutation that suppresses immune responses conditioned by the autoactivated R protein snc1 (for suppressor of npr1-1, constitutive 1). mos7-1 single mutant plants exhibit defects in basal and R protein-mediated immunity and in systemic acquired resistance but do not display obvious pleiotropic defects in development, salt tolerance, or plant hormone responses. MOS7 is homologous to human and Drosophila melanogaster nucleoporin Nup88 and resides at the nuclear envelope. In animals, Nup88 attenuates nuclear export of activated NF-kB transcription factors, resulting in nuclear accumulation of NF-kB. Our analysis shows that nuclear accumulation of snc1 and the defense signaling components Enhanced Disease Susceptibility 1 and Nonexpresser of PR genes 1 is significantly reduced in mos7-1 plants, while nuclear retention of other tested proteins is unaffected. The data suggest that specifically modulating the nuclear concentrations of certain defense proteins regulates defense outputs.

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Section: Discussionmentioning

confidence: 72%

“…Mutations or depletion of Nup88 in animals leads to increased nuclear export of NF-kB transcription factors (Uv et al, 2000;Xylourgidis et al, 2006; Takahashi et al, 2008). In Arabidopsis, CRM1-like transport is mediated by XPO1 (Haasen et al, 1999), a protein with homology to human CRM1.…”

Section: Nes-mediated Nuclear Protein Export Is Enhanced In Mos7-1mentioning

confidence: 99%

Nuclear Pore Complex Component MOS7/Nup88 Is Required for Innate Immunity and Nuclear Accumulation of Defense Regulators inArabidopsis

et al. 2009

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“…In metastatic melanoma cells overexpressing Nup88, constitutive NF-κB activation was found in the nucleus and cytoplasm, and Nup88 depletion reduced the tumor necrosis factor (TNF)-induced nuclear accumulation of NF-κB subunits in these cells. These phenomena imply that Nup88 overexpression in tumor cells may contribute to constitutive NF-κB activation [20] . In our previous study, almost 96% of acute monocytic leukemia U937 cells expressed Nup88 by flow cytometry analysis.…”

Section: Regulation Of Nucleoporin and Nucleophosminmentioning

confidence: 99%

New targets for the antitumor activity of gambogic acid in hematologic malignancies

Yang

Chen

2012

Acta Pharmacol Sin

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Gambogic acid (GA) is the main active ingredient of gamboge, a brownish to orange dry resin secreted from Garcinia hanburyi, a plant that is widely distributed in nature. Recent in vitro and in vivo studies have demonstrated that GA exerts potent antitumor effects against solid tumors of various derivations, and its antitumor mechanisms have been thoroughly investigated. On the other hand, normal cells remain relatively resistant to GA, indicating a therapeutic window. GA is currently in clinical trials in China. Over the last decade, our laboratory demonstrates that GA exhibits potent anticancer activities against hematological malignancies. This review focuses on the new mechanisms through which GA inhibits proliferation and induces apoptosis in malignant hematological cells. These include the regulation of expression and intracellular positioning of nucleoporin and nucleophosmin; downregulation of steroid receptor coactivator-3 (SRC-3) and its downstream proteins; upregulation of death inducer-obliterator (DIO-1); downregulation of HERG potassium channel; as well as induction of reactive oxygen species (ROS) accumulation.

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“…One nuclear pore complex protein, i.e., nuclear envelop protein 88 (NUP88), is frequently overexpressed in a number of cancers and associated with high-grade malignancies [4-6]. Overexpression of NUP88 impairs export-mediated downregulation of activated nuclear factor-κB [7]. Moreover, it is involved in proper mitotic spindle functioning [8].…”

Section: Introductionmentioning

confidence: 99%

<b><i>TMEM18</i></b>: A Novel Prognostic Marker in Acute Myeloid Leukemia

Kim

Han

et al. 2018

Acta Haematol

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Background: Certain nuclear envelope proteins are associated with important cancer cell characteristics, including migration and proliferation. Abnormal expression of and genetic changes in nuclear envelope proteins have been reported in acute myeloid leukemia (AML) patients. Transmembrane protein 18 (TMEM18), a nuclear envelope protein, is involved in neural stem cell migration and tumorigenicity. Methods: To examine the prognostic significance of TMEM18 in AML patients, we analyzed an AML cohort from The Cancer Genome Atlas (TCGA, n = 142). Results: Kaplan-Meier survival analysis revealed that TMEM18 overexpression was associated with a better AML prognosis with good discrimination (p = 0.019). Interestingly, this ability to predict the prognosis was significant in male AML patients, but not in female ones. C-index and area-under-the-curve analyses further supported this discriminative ability and multivariate analysis confirmed its prognostic significance (p = 0.00347). Correlation analysis revealed that TMEM18 had a statistically significant positive correlation with nuclear envelop protein 133 (NUP133), NUP35, NUP54, NUP62, and NUP88. Conclusion: Because the current AML prognostic factors do not take mRNA expression into consideration unlike other cancers, the development of mRNA-based prognostic factors would be beneficial for accurate prediction of the survival of AML patients. Therefore, TMEM18 gene is a potential biomarker for AML.

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Tumor marker nucleoporin 88kDa regulates nucleocytoplasmic transport of NF-κB

Cited by 41 publications

References 28 publications

Nuclear Pore Complex Component MOS7/Nup88 Is Required for Innate Immunity and Nuclear Accumulation of Defense Regulators inArabidopsis

Nuclear Pore Complex Component MOS7/Nup88 Is Required for Innate Immunity and Nuclear Accumulation of Defense Regulators inArabidopsis

New targets for the antitumor activity of gambogic acid in hematologic malignancies

<b><i>TMEM18</i></b>: A Novel Prognostic Marker in Acute Myeloid Leukemia

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