Inactivation of nucleolin leads to nucleolar disruption, cell cycle arrest and defects in centrosome duplication

Ugrinova, Iva; Monier, Karine; Ivaldi, Corinne; Thiry, Marc; Storck, Sébastien; Mongélard, Fabien; Bouvet, Philippe

doi:10.1186/1471-2199-8-66

Cited by 195 publications

(228 citation statements)

References 61 publications

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“…4), as it was shown to be the case after overexpressing a dominant negative form of ninein. 14 This nucleation delay is neither a consequence of NCL silenced cells accumulating in G2, 29 since the rate of microtubule nucleation is unchanged in G2 compared to G1. 39 Since purified nucleolin did not favor microtubule nucleation by itself (data not shown), we concluded that nucleolin might act as an activator of microtubule nucleation when bound to centrosomal gTuRC, thereby playing a role in the acquisition of mature markers on immature centrioles.…”

Section: Discussionmentioning

confidence: 99%

“…28,29 The presence of these supernumerary structures in interphase cells was analyzed in regards to PCM components like g-tubulin (Figs. 4A-E and K), pericentrin (Figs.…”

Section: Nucleolin Silencing Leads To Amplification Of Centriole Immamentioning

confidence: 99%

“…The depletion of nucleolin by RNA interference leads to reduced proliferation and increased apoptosis. 28,29 In interphase cells, the absence of nucleolin results in an increased nuclear size as well as numerous nuclear alterations. 28,29 Interestingly, when nucleolin-silenced cells reach mitosis, abnormal centrosome amplification is observed.…”

Section: Introductionmentioning

confidence: 99%

“…28,29 In interphase cells, the absence of nucleolin results in an increased nuclear size as well as numerous nuclear alterations. 28,29 Interestingly, when nucleolin-silenced cells reach mitosis, abnormal centrosome amplification is observed. 28,29 However, the molecular mechanism linking nucleolin to centrosome duplication regulation has not been elucidated to date.…”

Section: Introductionmentioning

confidence: 99%

“…28,29 Interestingly, when nucleolin-silenced cells reach mitosis, abnormal centrosome amplification is observed. 28,29 However, the molecular mechanism linking nucleolin to centrosome duplication regulation has not been elucidated to date. By proteomic analysis, nucleolin has been identified in human centrosomes 15 and mitotic spindles.…”

Section: Introductionmentioning

confidence: 99%

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Centrosomal nucleolin is required for microtubule network organization

et al. 2015

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Nucleolin is a pleiotropic protein involved in a variety of cellular processes. Although multipolar spindle formation has been observed after nucleolin depletion, the roles of nucleolin in centrosome regulation and functions have not been addressed. Here we report using immunofluorescence and biochemically purified centrosomes that nucleolin colocalized only with one of the centrioles during interphase which was further identified as the mature centriole. Upon nucleolin depletion, cells exhibited an amplification of immature centriole markers surrounded by irregular pericentrin staining; these structures were exempt from maturation markers and unable to nucleate microtubules. Furthermore, the microtubule network was disorganized in these cells, exhibiting frequent non-centrosomal microtubules. At the mature centriole a reduced kinetics in the centrosomal microtubule nucleation phase was observed in live silenced cells, as well as a perturbation of microtubule anchoring. Immunoprecipitation experiments showed that nucleolin belongs to protein complexes containing 2 key centrosomal proteins, g-tubulin and ninein, involved in microtubule nucleation and anchoring steps. Altogether, our study uncovered a new role for nucleolin in restricting microtubule nucleation and anchoring at centrosomes in interphase cells.

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Section: Discussionmentioning

confidence: 99%

“…28,29 The presence of these supernumerary structures in interphase cells was analyzed in regards to PCM components like g-tubulin (Figs. 4A-E and K), pericentrin (Figs.…”

Section: Nucleolin Silencing Leads To Amplification Of Centriole Immamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Centrosomal nucleolin is required for microtubule network organization

et al. 2015

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Downregulation of NCL attenuates tumor formation and growth in HeLa cells by targeting the PI3K/AKT pathway

Ying

Pan²,

Tang

et al. 2022

Cancer Medicine

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Background Nucleolin (NCL, C23) is a multifunctional phosphoprotein that plays a vital role in modulating the survival, proliferationand apoptosis of cancer cells. However, the effects of NCL on cervical cancer and the underlying mechanisms behind this are poorly understood. Methods Lentiviral transfection technology was used to construct NCL knockdown cell lines. MTT, colony formation assays, and tumorigenic assays in vivo were performed to observe cell proliferation. HOECHST 33342 staining, flow cytometry, and caspase activity assay were used to test cell apoptosis. RNA‐Seq, Western blotting, and RT‐PCR were conducted to investigate the specific molecular mechanism. Results NCL knockdown inhibited cell proliferation and promoted apoptosis both in vivo and in vitro. Mechanistic studies revealed that NCL knockdown inhibited the PI3K/AKT pathway by upregulating FGF, ITGA, TNXB, VEGF, Caspase 3, and Bax, as well as by downregulating AKT, GNB4, CDK6, IL6R, LAMA, PDGFD, PPP2RSA and BCL‐2. In addition, the expression levels of apoptosis‐related genes after using a PI3K inhibitor LY294002 were consistent with shRNA studies, while treatment with a 740Y‐P agonist showed the opposite effect. Conclusions Our findings indicate that downregulation of NCL may be a novel treatment strategy forcervical cancer.

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Modulatory effect of rRNA synthesis and ppUL83 nucleolar compartmentalization on human cytomegalovirus gene expression in vitro

Arcangeletti¹,

Rodighiero²,

Gatti³

et al. 2009

J of Cellular Biochemistry

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The nucleolus is a nuclear domain involved in the biogenesis of ribosomes, as well as in many other important cellular regulatory activities, such as cell cycle control and mRNA processing. Many viruses, including herpesviruses, are known to exploit the nucleolar compartment during their replication cycle. In a previous study, we demonstrated the preferential targeting and accumulation of the human cytomegalovirus (HCMV) UL83 phosphoprotein (pp65) to the nucleolar compartment and, in particular, to the nucleolar matrix of lytically infected fibroblasts; such targeting was already evident at very early times after infection. Here we have investigated the possible effects of rRNA synthesis inhibition upon the development of HCMV lytic infection, by using either actinomycin D or cisplatin at low concentrations, that are known to selectively inhibit RNA polymerase I activity, whilst leaving RNA polymerase II function unaffected. Following the inhibition of rRNA synthesis by either of the agents used, we observed a significant redistribution of nucleolar proteins within the nucleoplasm and a simultaneous depletion of viral pp65 from the nucleolus; this effect was highly evident in both unextracted cells and in nuclear matrices in situ. Of particular interest, even a brief suppression of rRNA synthesis resulted in a very strong inhibition of the progression of HCMV infection, as was concluded from the absence of accumulation of HCMV major immediate-early proteins within the nucleus of infected cells. These data suggest that a functional relationship might exist between rRNA synthesis, pp65 localization to the nucleolar matrix and the normal development of HCMV lytic infection.

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Inactivation of nucleolin leads to nucleolar disruption, cell cycle arrest and defects in centrosome duplication

Cited by 195 publications

References 61 publications

Centrosomal nucleolin is required for microtubule network organization

Centrosomal nucleolin is required for microtubule network organization

Downregulation of NCL attenuates tumor formation and growth in HeLa cells by targeting the PI3K/AKT pathway

Modulatory effect of rRNA synthesis and ppUL83 nucleolar compartmentalization on human cytomegalovirus gene expression in vitro

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