Multifaceted Nucleolin Protein and Its Molecular Partners in Oncogenesis

Ugrinova, Iva; Petrova, Maria; Chalabi-Dchar, Mounira; Bouvet, Philippe

doi:10.1016/bs.apcsb.2017.08.001

Cited by 62 publications

(49 citation statements)

References 157 publications

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“…In vitro and in vivo studies revealed that oncogenic effects of NCL can have multimodal origins reflecting the multifunctional properties of NCL in the different subcellular compartments [ 4 ]. Following this line, it has been reported that decrease of NCL mRNA levels mainly reduced expression of surface and cytoplasmic NCL protein without affecting the one of nuclear NCL [ 5 ], suggesting that depending on NCL expression levels distinct functions of NCL could be involved.…”

Section: Discussionmentioning

confidence: 99%

“…NCL is hence involved in numerous biological functions controlling cellular homeostasis through modulation of cell proliferation, apoptosis, and cell survival. Recent studies also demonstrated the role of NCL in angiogenesis, epithelial-to-mesenchymal transition, and stemness [ 3 , 4 ]. In agreement with NCL properties, several in vitro and in vivo studies had reported an oncogenic effect of NCL that appears to be multifactorial, reflecting its multiple functions [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

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Druggable Nucleolin Identifies Breast Tumours Associated with Poor Prognosis That Exhibit Different Biological Processes

Long

Lardy-Cléaud

Bray

et al. 2018

Cancers

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Background: Nucleolin (NCL) is a multifunctional protein with oncogenic properties. Anti-NCL drugs show strong cytotoxic effects, including in triple-negative breast cancer (TNBC) models, and are currently being evaluated in phase II clinical trials. However, few studies have investigated the clinical value of NCL and whether NCL stratified cancer patients. Here, we have investigated for the first time the association of NCL with clinical characteristics in breast cancers independently of the different subtypes. Methods: Using two independent series (n = 216; n = 661), we evaluated the prognostic value of NCL in non-metastatic breast cancers using univariate and/or multivariate Cox-regression analyses. Results: We reported that NCL mRNA expression levels are markers of poor survivals independently of tumour size and lymph node invasion status (n = 216). In addition, an association of NCL expression levels with poor survival was observed in TNBC (n = 40, overall survival (OS) p = 0.0287, disease-free survival (DFS) p = 0.0194). Transcriptomic analyses issued from The Cancer Genome Atlas (TCGA) database (n = 661) revealed that breast tumours expressing either low or high NCL mRNA expression levels exhibit different gene expression profiles. These data suggest that tumours expressing high NCL mRNA levels are different from those expressing low NCL mRNA levels. Conclusions: NCL is an independent marker of prognosis in breast cancers. We anticipated that anti-NCL is a promising therapeutic strategy that could rapidly be evaluated in high NCL-expressing tumours to improve breast cancer management.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Druggable Nucleolin Identifies Breast Tumours Associated with Poor Prognosis That Exhibit Different Biological Processes

Long

Lardy-Cléaud

Bray

et al. 2018

Cancers

Self Cite

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“…Ncl could be characterized as a moonlighting protein [3,4] as it is able to perform multiple and unrelated functions without partitioning these functions into different protein domains. Indeed, the central domain of Ncl composed of 4 classical RNA-Binding domains (RBD) allow the interaction of Ncl with numerous nucleic acids sequences (RNA and DNA) involving Ncl in diverse functions, such as pre-ribosomal RNA maturation, mRNA stability, mRNA translation regulation, transcriptional regulation of specific genes [5,6].…”

Section: Introductionmentioning

confidence: 99%

Nucleolin Interacts and Co-Localizes with Components of Pre-Catalytic Spliceosome Complexes

Ugrinova¹,

Chalabi-Dchar²,

Monier³

et al. 2019

Sci

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Nucleolin is an RNA binding protein that is involved in many post-transcriptional regulation steps of messenger RNAs in addition to its nucleolar role in ribosomal RNA transcription and assembly in pre-ribosomes. Acetylated nucleolin was found to be associated with nuclear speckles and to co-localize with the splicing factor SC35. Previous nuclear pull down of nucleolin identified several splicing components and factors involved in RNA polymerase II transcription associated with nucleolin. In this report, we show that these splicing components are specifics of the pre-catalytic A and B spliceosomes, while proteins recruited in the Bact, C and P complexes are absent from the nucleolin interacting proteins. Furthermore, we show that acetylated nucleolin co-localized with P-SF3B1, a marker of co-transcriptional active spliceosomes. P-SF3B1 complexes can be pulled down with nucleolin specific antibodies. Interestingly, the alternative splicing of Fibronectin at the IIICS and EDB sites was affected by nucleolin depletion. These data are consistent with a model where nucleolin could be a factor bridging RNA polymerase II transcription and assembly of pre-catalytic spliceosome similarly to its function in the co-transcriptional maturation of pre-rRNA.

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“…This nucleolar protein is of particular interest for several reasons. First, due to its aberrant expression NCL represents an ideal target for cancer therapy in several aggressive types of malignancies 27,28 . Second, NCL is an RNAbinding protein involved in processing and stabilization of coding and non-coding RNA, which would expand the potential involvement of RanBP9 in RNA metabolism.…”

Section: Discussionmentioning

confidence: 99%

Tagging enhances histochemical and biochemical detection of Ran Binding Protein 9 in vivo and reveals its interaction with Nucleolin

Soliman

Stark

Gardner

et al. 2019

Preprint

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AbstractThe lack of tools to reliably detect RanBP9 in vivo has significantly hampered progress in understanding the biological functions of this scaffold protein. We report here the generation of a novel mouse strain, RanBP9-TT, in which the endogenous protein is fused with a double (V5-HA) epitope tag at the C-terminus. We show that the double tag does not interfere with the essential functions of RanBP9. In contrast to RanBP9 constitutive knock-out animals, RanBP9-TT mice are viable, fertile and do not show any obvious phenotype. The V5-HA tag allows unequivocal detection of RanBP9 both by IHC and WB. Importantly, immunoprecipitation and mass spectrometry analyses reveal that the tagged protein pulls down known interactors of wild type RanBP9. Thanks to the increased detection power, we are also unveiling a novel interaction with Nucleolin, a prominent nucleolar protein.In summary, we report the generation of a new mouse line in which RanBP9 expression and interactions can be reliably studied by the use of commercially available αtag antibodies. The use of this line will help to overcome some of the existing limitations in the study of RanBP9 and potentially reveal novel functions of this protein in vivo such as those linked to Nucleolin.

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Multifaceted Nucleolin Protein and Its Molecular Partners in Oncogenesis

Cited by 62 publications

References 157 publications

Druggable Nucleolin Identifies Breast Tumours Associated with Poor Prognosis That Exhibit Different Biological Processes

Druggable Nucleolin Identifies Breast Tumours Associated with Poor Prognosis That Exhibit Different Biological Processes

Nucleolin Interacts and Co-Localizes with Components of Pre-Catalytic Spliceosome Complexes

Tagging enhances histochemical and biochemical detection of Ran Binding Protein 9 in vivo and reveals its interaction with Nucleolin

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