CNBP modulates the transcription of Wnt signaling pathway components

Margarit, Ezequiel; Armas, Pablo; Siburu, Nicolás García; Calcaterra, Nora B.

doi:10.1016/j.bbagrm.2014.08.009

Cited by 25 publications

(35 citation statements)

References 48 publications

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“…CNBP has also been proposed to exhibit various biological functions as a nucleic acid chaperone, such as regulating the transcription of c-myc, wnt , or skeletal muscle chloride channel 1 ( clc1 ), and inhibiting the translation of ribosomal protein mRNAs (rp-mRNAs) (2–6). Furthermore, CNBP has been largely implicated in various human diseases, including myotonic dystrophy type 2 (DM2) and sporadic inclusion body myositis (sIBM) (7,8).…”

Section: Introductionmentioning

confidence: 99%

CNBP acts as a key transcriptional regulator of sustained expression of interleukin-6

Lee

Kim

et al. 2017

Nucleic Acids Research

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The transcription of inflammatory genes is an essential step in host defense activation. Here, we show that cellular nucleic acid-binding protein (CNBP) acts as a transcription regulator that is required for activating the innate immune response. We identified specific CNBP-binding motifs present in the promoter region of sustained inflammatory cytokines, thus, directly inducing the expression of target genes. In particular, lipopolysaccharide (LPS) induced cnbp expression through an NF-κB-dependent manner and a positive autoregulatory mechanism, which enables prolonged il-6 gene expression. This event depends strictly on LPS-induced CNBP nuclear translocation through phosphorylation-mediated dimerization. Consequently, cnbp-depleted zebrafish are highly susceptible to Shigella flexneri infection in vivo. Collectively, these observations identify CNBP as a key transcriptional regulator required for activating and maintaining the immune response.

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Section: Introductionmentioning

confidence: 99%

CNBP acts as a key transcriptional regulator of sustained expression of interleukin-6

Lee

Kim

et al. 2017

Nucleic Acids Research

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“…14 This mild condition may explain the absence of significant differences not only in the relative abundance of cnbp transcripts but also in the expression of its targets, tbx2b and tcf7l2 . 23, 36 Nevertheless, the strong statistical correlation between CNBP and TCOF1 expression in human mesenchymal cells further supports the hypothesis of a functional link between these two genes in the pathology of TCS. This hypothesis is strengthened by the finding that increased expression of cnbp rescued the aberrant craniofacial phenotype of TCS -like zebrafish in a dose-dependent manner.…”

Section: Discussionmentioning

confidence: 55%

“…Among other alterations, 14 we found that the triangular area delimited by the Meckel cartilage, the length of the palatoquadrate-hyosymplectic (PQ), the length of the ceratohyal cartilages, the distance between ceratohyal cartilages joint and lateral fins and the length of the head (estimated by the distance from the most anterior Meckel to the point where the lateral fins start) showed, compared with controls, statistically significant reductions in TRA-morphants (see below and Figures 2d–h). These types of measurements have been used by us 23 and others 24 to describe craniofacial phenotypes affecting cartilages. The phenotype described here is exhibited by the mutant ( nolc1 hi4050Tg , http://zfin.org/action/genotype/view/ZDB-GENO-050809-6) and is in agreement with the phenotypes and findings described in both the human syndrome and in the Tcof1 +/− mouse model.…”

Section: Resultsmentioning

confidence: 99%

“…To repress tcof1 mRNA translation, TRA-MO (5′-TAGGAACCGTGCTGTCCTCCGCCAT-3′) was used at the concentration of 0.5 pmol/embryo (4 ng/embryo) in 5 nl as previously reported. 21, 23 As a control, STD-MO (5′-CCTCTTACCTCAGTTACAATTTATA-3′) was injected. ATG Tp53 was used as described in Ning et al 25 Cnbp TRA and Cnbp SPL were used as described.…”

Section: Methodsmentioning

confidence: 99%

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Cnbp ameliorates Treacher Collins Syndrome craniofacial anomalies through a pathway that involves redox-responsive genes

et al. 2016

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Treacher Collins Syndrome (TCS) is a rare congenital disease (1:50 000 live births) characterized by craniofacial defects, including hypoplasia of facial bones, cleft palate and palpebral fissures. Over 90% of the cases are due to mutations in the TCOF1 gene, which codifies the nucleolar protein Treacle. Here we report a novel TCS-like zebrafish model displaying features that fully recapitulate the spectrum of craniofacial abnormalities observed in patients. As it was reported for a Tcof1+/− mouse model, Treacle depletion in zebrafish caused reduced rRNA transcription, stabilization of Tp53 and increased cell death in the cephalic region. An increase of ROS along with the overexpression of redox-responsive genes was detected; furthermore, treatment with antioxidants ameliorated the phenotypic defects of craniofacial anomalies in TCS-like larvae. On the other hand, Treacle depletion led to a lowering in the abundance of Cnbp, a protein required for proper craniofacial development. Tcof1 knockdown in transgenic zebrafish overexpressing cnbp resulted in barely affected craniofacial cartilage development, reinforcing the notion that Cnbp has a role in the pathogenesis of TCS. The cnbp overexpression rescued the TCS phenotype in a dose-dependent manner by a ROS-cytoprotective action that prevented the redox-responsive genes' upregulation but did not normalize the synthesis of rRNAs. Finally, a positive correlation between the expression of CNBP and TCOF1 in mesenchymal cells from both control and TCS subjects was found. Based on this, we suggest CNBP as an additional target for new alternative therapeutic treatments to reduce craniofacial defects not only in TCS but also in other neurocristopathies.

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“…Furthermore, studies have shown that CNBP acts as a nucleic acid chaperone with both single-strand DNAand RNA-binding activity (Michelotti et al 1995, Yasuda et al 1995, Armas et al 2008b. For example, CNBP activates c-myc transcription both in vivo and in vitro (Shimizu et al 2003, Armas et al 2008a; data from Armas et al and Margarit et al indicate that CNBP modulates the transcription of Wnt signaling pathway components (Wnt5b, Cdk14, Ptk7 and Tcf7l2) (Armas et al 2013, Margarit et al 2014. Wnt signaling is a highly conserved cell-to-cell communication mechanism, including canonical and noncanonical branches.…”

Section: Introductionmentioning

confidence: 99%

Cellular nucleic acid-binding protein is vital to testis development and spermatogenesis in mice

Zheng

Guo

et al. 2018

Reproduction

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The cellular nucleic acid-binding protein (CNBP), also known as zinc finger protein 9, is a highly conserved zinc finger protein that is strikingly conserved among vertebrates. Data collected from lower vertebrates showed that CNBP is expressed at high levels and distributed in the testes during spermatogenesis. However, the location and function of CNBP in mammalian testes are not well known. Here, by neonatal mouse testis culture and spermatogonial stem cells (SSC) culture methods, we studied the effect of CNBP knockdown on neonatal testicular development. Our results revealed that CNBP was mainly located in the early germ cells and Sertoli cells. Knockdown of CNBP using morpholino in neonatal testis culture caused disruption of seminiferous tubules, mislocation of Sertoli cells and loss of germ cells, which were associated with the aberrant Wnt/β-catenin pathway activation. However, knockdown of CNBP in SSC culture did not affect the survival of germ cells. In conclusion, our study suggests that CNBP could maintain testicular development by inhibiting the Wnt/β-catenin pathway, particularly by influencing Sertoli cells.

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CNBP modulates the transcription of Wnt signaling pathway components

Cited by 25 publications

References 48 publications

CNBP acts as a key transcriptional regulator of sustained expression of interleukin-6

CNBP acts as a key transcriptional regulator of sustained expression of interleukin-6

Cnbp ameliorates Treacher Collins Syndrome craniofacial anomalies through a pathway that involves redox-responsive genes

Cellular nucleic acid-binding protein is vital to testis development and spermatogenesis in mice

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