Nucleoporin 62-Like Protein Activates Canonical Wnt Signaling through Facilitating the Nuclear Import of β-Catenin in Zebrafish

Yang, Xiaojie; Gu, Qilin; Lin, Li; Li, Shaoyang; Zhong, Shan; Li, Qing; Cui, Zongbin

doi:10.1128/mcb.01181-14

Cited by 33 publications

(38 citation statements)

References 108 publications

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“…The malignant activation of the Wnt signaling pathway leads to the onset of multiple types of cancers20. Meanwhile, β-catenin is a key activator of the canonical Wnt signaling pathway21. The abnormal accumulation and nuclear translocation of β-catenin play an important role in all of the β-catenin mutations22.…”

Section: Discussionmentioning

confidence: 99%

BHX Inhibits the Wnt Signaling Pathway by Suppressing β-catenin Transcription in the Nucleus

Ding

Wang

et al. 2016

Sci Rep

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BHX (N-(4-hydroxybenzyl)-1,3,4-triphenyl-4,5-dihydro-1H-pyrazole-5-carboxamide), a Wnt signaling pathway inhibitor, effectively inhibits tumor cell growth, but the underlying mechanism is unclear. Thus, we aim to investigate the effects and associated mechanism of BHX action on A549 and MCF-7 cell lines. In our study, MTT(3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide) and xenograft model assay indicated that cell growth was inhibited by BHX at a range of concentrations in vitro and in vivo. The expression of β-catenin and Wnt signaling pathway downstream target genes were decreased evidently under BHX treatment. Flow cytometry also revealed that BHX treatment significantly induced G1 arrest. Further analysis showed that BHX lowered the transcriptional level of β-catenin. In conclusion, BHX inhibited the nuclear synthesis of β-catenin, thereby suppressing the Wnt signaling pathway and further inhibiting tumor growth and proliferation.

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Section: Discussionmentioning

confidence: 99%

BHX Inhibits the Wnt Signaling Pathway by Suppressing β-catenin Transcription in the Nucleus

Ding

Wang

et al. 2016

Sci Rep

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“…We further created pCMV-Tag2C-RING1A-C398A using a PCR-based method 11, 12 . Briefly, PCR reaction was performed using primer pair: C398A Mutation-Forward (5′-CGGCCACTGGAGCTGGCCTATGCTCCCACCAAGGATCCAAAG-3′) and C398A Mutation-Reverse (5′-TTGGTGGGAGCATAGGCCAGCTCCAGTGGCCGGGACAC-3′).…”

Section: Methodsmentioning

confidence: 99%

Transdifferentiation Requires iNOS Activation

Meng

Zhou

et al. 2016

Circulation Research

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Rationale We have previously shown that innate immunity is necessary for transdifferentiation of fibroblasts to endothelial cells. A major signaling molecule involved in innate immunity is inducible nitric oxide synthase (iNOS). Accordingly, we hypothesized that iNOS-generated nitric oxide (NO) might enhance transdifferentiation. Objective To elucidate the role of NO in epigenetic plasticity during transdifferentiation. Methods and Results We exposed the BJ fibroblasts to transdifferentiation formulation that included endothelial growth factors and innate immune activator polyinosinic:polycytidylic acid (PIC) to induce endothelial cells (iECs). Generation of iECs was associated with iNOS expression and NO elaboration. In absence of PIC, or in presence of antagonists of NFκB or iNOS activity, NO synthesis and iEC generation was reduced. Furthermore, genetic knockout (in MEFs) or siRNA knockdown (in BJ fibroblasts) of iNOS nearly abolished transdifferentiation, an effect which could be reversed by iNOS overexpression. Notably, PIC induced nuclear localization of iNOS, and its binding to, and nitrosylation of, the epigenetic modifier RING1A as assessed by immunostaining, Co-IP and mass spectrometry. Nitrosylation of RING1A reduced its binding to chromatin, and reduced global levels of repressive histone marker H3K27trimethylation. Overexpression of a mutant form of RING1A (C398A) lacking the nitrosylation site almost abrogated transdifferentiation. Conclusions Overall, our data indicates that during transdifferentiation, innate immune activation increases iNOS generation of NO to S-nitrosylate RING1A, a key member of the polycomb repressive complex. Nitrosylation of RING1A reduces its binding to chromatin and decreases H3K27trimethylation level. The release of epigenetic repression by nitrosylation of RING1A is critical for effective transdifferentiation.

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“…More importantly, nuclear levels of activated Dorsal were reduced in response to infection when Nup88 is deleted (Uv et al, 2000). Nup88 (Genenncher et al, 2016) along with other nucleoporins like Nup62 (Yang et al, 2015), Nup153 and Nup214 (Xu et al, 2002) are shown to be critical in developmental pathways, but detailed analyses emphasizing on their involvement in selective nuclear translocation of activated signals. In contrast, we report sustained activation of NF-B signaling and its accumulation inside the nucleus only upon dElys depletion but not with other nucleoporins involved nuclear pore complex assembly.…”

Section: Discussionmentioning

confidence: 99%

ELYS coordinates NF-κB pathway dynamics during development inDrosophila

Mehta

Kumar

Mishra

2018

Preprint

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Nuclear pores are the exclusive conduit to facilitate the nucleocytoplasmic transport in a precisely regulated manner. ELYS, a constituent protein of nuclear pores, initiates assembly of nuclear pore complexes (NPCs) into functional nuclear pores towards the end of mitosis. Using cellular, molecular and genetic tools, here, we report that ELYS orthologue (dElys) plays critical roles during Drosophila development. Through in silico analyses, we find all conserved structural features in dElys except for the presence of non-canonical AT-hook motif strongly binding with DNA. dElys localized to nuclear rim in interphase cells, but during mitosis, it was present on chromatin. RNAi mediated depletion of dElys leads to aberrant development and defects in the nuclear lamina and NPCs assembly at the cellular level. Furthermore, we demonstrate that in dElys depletion NF-B is activated and accumulates inside the nucleus which results in illtimed expression of critical molecules. dElys depletion sustains NF-B into the nucleus in post-embryonic stages. Prolonged NF-B inside nucleus induces apoptosis in response to hitherto unknown quality check mechanism and highlights on the underappreciated apoptotic paradigm of NF-B pathway.

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Nucleoporin 62-Like Protein Activates Canonical Wnt Signaling through Facilitating the Nuclear Import of β-Catenin in Zebrafish

Cited by 33 publications

References 108 publications

BHX Inhibits the Wnt Signaling Pathway by Suppressing β-catenin Transcription in the Nucleus

BHX Inhibits the Wnt Signaling Pathway by Suppressing β-catenin Transcription in the Nucleus

Transdifferentiation Requires iNOS Activation

ELYS coordinates NF-κB pathway dynamics during development inDrosophila

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