Differential effects of <i>Nucleostemin</i> suppression on cell cycle arrest and apoptosis in the bladder cancer cell lines 5637 and SW1710

Nikpour, Parvaneh; Mowla, Seyed Javad; Jafarnejad, Seyed Mehdi; Fischer, Ute; Schulz, Wolfgang A.

doi:10.1111/j.1365-2184.2009.00635.x

Cited by 34 publications

(23 citation statements)

References 30 publications

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“…Studies that reported a G1/S arrest phenotype following nucleostemin-knockdown include those performed in U2OS cells (Dai et al, 2008;Ma and Pederson, 2007), SW1710 cells (Nikpour et al, 2009), HeLa cells (Sijin et al, 2004), PC-3 cells (Liu et al, 2010) and bone marrow-derived stromal stem cells (Jafarnejad et al, 2008). In contrast, the finding that nucleostemin-depleted cells are arrested at the G2/M phase has also been reported in several studies performed in U2OS cells (Meng et al, 2008), HeLa cells (Romanova et al, 2009), 5637 cells (Nikpour et al, 2009) and mouse embryonic fibroblast cells (MEFs) (Zhu et al, 2006). It is noted that the studies describing G1/S arrest used cells with either wild-type or mutant forms of p53, retinoblastoma, p16 and alternate reading frame (p14ARF) protein (both encoded by CDKN2A), and studies describing G2/M arrest also used cells with wild-type or mutant forms of p53, retinoblastoma, p16 and p14ARF.…”

Section: The Amazing Diversity Of Cell-cycle-arrest Profiles Of Nuclementioning

confidence: 99%

Turning a new page on nucleostemin and self-renewal

Tsai

2014

Journal of Cell Science

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A quintessential trait of stem cells is embedded in their ability to selfrenew without incurring DNA damage as a result of genome replication. One key self-renewal factor is the nucleolar GTPbinding protein nucleostemin (also known as guanine-nucleotidebinding protein-like 3, GNL3, in invertebrate species). Several studies have recently pointed to an unexpected role of nucleostemin in safeguarding the genome integrity of stem and cancer cells. Since its discovery, the predominant presence of nucleostemin in the nucleolus has led to the notion that it might function in the cardcarrying event of the nucleolus -the biogenesis of ribosomes. As tantalizing as this might be, a ribosomal role of nucleostemin is refuted by evidence from recent studies, which argues that nucleostemin depletion triggers a primary event of DNA damage in S phase cells that then leads to ribosomal perturbation. Furthermore, there have been conflicting reports regarding the p53 dependency of nucleostemin activity and the cell cycle arrest profile of nucleostemindepleted cells. In this Commentary, I propose a model that explains how the many contradictory observations surrounding nucleostemin can be reconciled and suggest that this protein might not be as multitasking as has been previously perceived. The story of nucleostemin highlights the complexity of the underlying molecular events associated with the appearance of any cell biological phenotype and also signifies a new understanding of the genome maintenance program in stem cells.

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Section: The Amazing Diversity Of Cell-cycle-arrest Profiles Of Nuclementioning

confidence: 99%

Turning a new page on nucleostemin and self-renewal

Tsai

2014

Journal of Cell Science

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“…Furthermore, Nikpour et al [19] were found over-expression of nucleostemin in the most uroepithelial carcinoma cell lines. They suggest involvement of nucleostemin differs even between tumors of the same type, like invasive bladder cancers.…”

Section: Discussionmentioning

confidence: 97%

Comparison of nucleostemin gene expression in CD133+ and CD133− cell population in colon cancer cell line HT29

et al. 2014

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“…Effects shown include a G1/S arrest (Dai et al, 2008;Ma and Pederson, 2007;Nikpour et al, 2009) 2009; Romanova et al, 2009a;Zhu et al, 2006). This discrepancy cannot be explained by the status of p53, Rb or p16 in the cell models used.…”

Section: The Effect Of Nucleostemin Depletion On Cell-cycle Progressionmentioning

confidence: 92%

Distinct genome protective vs. ribosome synthetic functions of the paralogous nucleolar proteins nucleostemin and GNL3L

Lin

Meng

Lin

et al. 2014

Journal of Cell Science

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The mammalian nucleolar proteins nucleostemin and GNL3-like (GNL3L) are encoded by paralogous genes that arose from an ancestral invertebrate gene, GNL3. Invertebrate GNL3 has been implicated in ribosome biosynthesis, as has its mammalian descendent, GNL3L. The paralogous mammalian nucleostemin protein has, instead, been implicated in cell renewal. Here, we found that depletion of nucleostemin in a human breast carcinoma cell line triggers prompt and significant DNA damage in S-phase cells without perturbing the initial step of ribosomal (r)RNA synthesis and only mildly affects the total ribosome production. By contrast, GNL3L depletion markedly impairs ribosome production without inducing appreciable DNA damage. These results indicate that, during vertebrate evolution, GNL3L retained the role of the ancestral gene in ribosome biosynthesis, whereas the paralogous nucleostemin acquired a novel genome-protective function. Our results provide a coherent explanation for what had seemed to be contradictory findings about the functions of the invertebrate versus vertebrate genes and are suggestive of how the nucleolus was fine-tuned for a role in genome protection and cell-cycle control as the vertebrates evolved.

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Differential effects of Nucleostemin suppression on cell cycle arrest and apoptosis in the bladder cancer cell lines 5637 and SW1710

Cited by 34 publications

References 30 publications

Turning a new page on nucleostemin and self-renewal

Turning a new page on nucleostemin and self-renewal

Comparison of nucleostemin gene expression in CD133+ and CD133− cell population in colon cancer cell line HT29

Distinct genome protective vs. ribosome synthetic functions of the paralogous nucleolar proteins nucleostemin and GNL3L

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