The moving parts of the nucleolus

Olson, Matthew S.; Dundr, Miroslav

doi:10.1007/s00418-005-0754-9

Cited by 187 publications

(181 citation statements)

References 81 publications

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“…The expression levels of these proteins correlate with the tumorigenicity of MCF-7 cells that express mutant p14. In recent years, it has been established that in addition to its role in rRNA synthesis and ribosome biogenesis, the nucleolus is involved in a variety of cellular functions, including regulation of the cell cycle, senescence, gene silencing, and sensing of cellular stress (26)(27)(28)(29)(30)(31), as well as in viral replication (32,33). The relationship between the nucleolus, ribosome biogenesis, and cancer has been the topic of a recent review (34), in which some evidence to that effect has been documented.…”

Section: Discussionmentioning

confidence: 99%

The Signal Peptide of Mouse Mammary Tumor Virus-Env: A Phosphoprotein Tumor Modulator

Feldman

Roniger

Bar-Sinai

et al. 2012

Molecular Cancer Research

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Mouse mammary tumor virus (MMTV) is associated primarily with mammary carcinomas and lymphomas. The signal peptide of the MMTV envelope precursor is uniquely targeted to nucleoli of cells that harbor the virus, where it can function as a nuclear export factor for intron-containing transcripts. Antibodies to this signal peptide, which we refer to as p14, were previously shown to label nucleoli in a subset of human breast cancers. To look for additional cellular functions of p14, different mutants were ectopically expressed in the MCF-7 human breast cancer cell line. This approach identified motifs responsible for its nucleolar targeting, nucleocytoplasmic shuttling, target protein (B23, nucleophosmin) binding, and phosphorylation at serine 18 and 65 both in situ and in vitro. To test the role of these phosphorylation sites, we carried out in vivo tumorigenesis studies in severe combined immunodeficient mice. The findings show that the p14-Ser65Ala mutation is associated with impaired tumorigenicity, whereas the p14-Ser18Ala mutation is associated with enhanced tumorigenicity. Microarray analysis suggests that phosphorylation at serine 18 or at serine 65 is associated with transcriptional regulation of the L5 nucleolar ribosomal protein (a p14 target) and the Erb-B signal transduction pathway. Taken together, these results show that the phosphorylation status of p14 determines whether it functions as a pro-oncogenic or antioncogenic modulator.

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Section: Discussionmentioning

confidence: 99%

The Signal Peptide of Mouse Mammary Tumor Virus-Env: A Phosphoprotein Tumor Modulator

Feldman

Roniger

Bar-Sinai

et al. 2012

Molecular Cancer Research

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“…In reality, the structure of a nucleolus is the total sum of the molecules entering and leaving a given subnuclear space, with the residence times of individual molecules governing its overall organization (Olson and Dundr, 2005). These residence times are determined by interactions between nucleolar molecules.…”

Section: Journal Of Cell Science 2102mentioning

confidence: 99%

Nucleolin functions in nucleolus formation and chromosome congression

Matsunaga

Takata

et al. 2007

Journal of Cell Science

120

124

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A complex structure, designated the chromosome periphery, surrounds each chromosome during mitosis. Although several proteins have been shown to localize to the chromosome periphery, their functions during mitosis remain unclear. Here, we used a combination of highresolution microscopy and RNA-interference-mediated depletion to study the functions of nucleolin, a nucleolar protein localized at the chromosome periphery, in interphase and mitosis. During mitosis, nucleolin was localized in the peripheral region including the vicinity of the outer kinetochore of chromosomes. Staining with an antibody specific for nucleolin phosphorylated by CDC2 revealed that nucleolin was also associated with the spindle poles from prometaphase to anaphase. Nucleolin depletion resulted in disorganization of the nucleoli at interphase. Furthermore, nucleolin-depleted cells showed a prolonged cell cycle with misaligned chromosomes and defects in spindle organization. The misaligned chromosomes showed syntelic kinetochore-microtubule attachments with reduced centromere stretching. Taken together, our results indicate that nucleolin is required for nucleolus formation, and is also involved in chromosome congression and spindle formation. Journal of Cell Science 2092Nucleolin is an abundant nucleolar protein localized in the DFCs and GCs of nucleoli (Biqqioqera et al., 1990). Nucleolin plays essential roles in rDNA transcription, rRNA maturation, ribosome assembly and nucleocytoplasmic transport (Ginisty et al., 1999;Srivastava and Pollard, 1999). As a multifunctional protein, nucleolin has also been proposed to be a nuclear matrix-binding protein (Gotzmann et al., 1997), to interact with telomerase (Khurts et al., 2004) and to be involved in the regulation of apoptosis (Mi et al., 2003), intestinal cell differentiation (Turck et al., 2006) and remodeling of nucleosomes (Angelov et al., 2006). Although many functions of nucleolin have been clarified, previous studies have fallen short of demonstrating its functions during mitosis.Nucleolin is highly phosphorylated (Olson et al., 1975;Rao et al., 1982) and its phosphorylation is highly regulated during the cell cycle (Peter et al., 1990;Morimoto et al., 2005). Extensive phosphorylation by casein kinase 2 (CK2) occurs at interphase and by CDC2 during mitosis (Peter et al., 1990), and this regulated phosphorylation of nucleolin probably regulates nucleolin functions during the cell cycle (Ginisty et al., 1999). It has been demonstrated that phosphorylation of nucleolin at interphase is correlated with active rRNA transcription (Suzuki et al., 1987). Despite a previous study describing the localization of nucleolin phosphorylated by CDC2 (Dranovsky et al., 2001), no information about its functions during mitosis has been obtained to date.Here, we demonstrate that nucleolin localizes to the nucleoli, which are located in the peripheral region including the vicinity of the outer kinetochore of chromosomes, in interphase nuclei and during mitosis. Staining with an antibody specific for nucle...

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“…Indeed, an increasing data showed that many proteins unrelated to ribosome assembly, including viral proteins encoded by DNA and RNA viruses [16], were detected in the nucleolus. Thus, many non-traditional functions of the nucleolus have been proposed [5][6][7]9]. These include signal recognition particle assembly, small RNA modification, RNA editing, telomerase maturation, nuclear export, cell cycle control, and stress sensor [17][18][19][20][21][22].…”

Section: Plurifunctionality Of the Nucleolusmentioning

confidence: 99%

“…However, to understand the structure and function of nucleolus then took more than one century. Till 1960s, two major progresses in nucleolus research have been accumulated and summarized as follows: (i) the nucleolus is membrane-less structure and appears fibril and granule, which are recognized as a tripartite structure, including the dense fibrillar component (DFC), the fibrillar center (FC), and the granular component (GC), under an electron microscope [4][5][6] ( Figure 1B); and (ii) it is the site for pre-rRNA transcription and processing and for ribosome subunit assembly and thus known as a "factory of ribosome" [5][6][7][8]. On the other hand, the dynamic disappearance and reappearance of nucleoli in mitotic cells were described in 1893 and 1894 [4].…”

Section: Introductionmentioning

confidence: 99%

“…owing to the application of green and red fluorescence proteins (GFP and RFP) in living cells and the discovery of subnuclear compartments (speckles and paraspeckles) by various antibodies, using time-lapsing and confocal microscopy [6]. At the same period of time, new functions, of the nucleolus, in addition to the ribosome biogenesis, which are called non-traditional or non-conventional functions, were emerged [5,9,10].…”

Section: Introductionmentioning

confidence: 99%

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