The cell center, consisting of a pair of CENTRIOLES surrounded by a cloud of amorphous material called the pericentriolar region. During interphase, the centrosome nucleates microtubule outgrowth. The centrosome duplicates and, during mitosis, separates to form the two poles of the mitotic spindle (MITOTIC SPINDLE APPARATUS).
Self-replicating, short, fibrous, rod-shaped organelles. Each centriole is a short cylinder containing nine pairs of peripheral microtubules, arranged so as to form the wall of the cylinder.
A microtubule structure that forms during CELL DIVISION. It consists of two SPINDLE POLES, and sets of MICROTUBULES that may include the astral microtubules, the polar microtubules, and the kinetochore microtubules.
Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein TUBULIN and are influenced by TUBULIN MODULATORS.
A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.
A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from SPERM FLAGELLUM; CILIA; and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to COLCHICINE; VINCRISTINE; and VINBLASTINE.
An amorphous region of electron dense material in the cytoplasm from which the MICROTUBULES polymerization is nucleated. The pericentriolar region of the CENTROSOME which surrounds the CENTRIOLES is an example.
High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.
A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. They are involved in many aspects of cell division, including centrosome duplication, SPINDLE APPARATUS formation, chromosome alignment, attachment to the spindle, checkpoint activation, and CYTOKINESIS.
The interval between two successive CELL DIVISIONS during which the CHROMOSOMES are not individually distinguishable. It is composed of the G phases (G1 PHASE; G0 PHASE; G2 PHASE) and S PHASE (when DNA replication occurs).
An aurora kinase that localizes to the CENTROSOME during MITOSIS and is involved in centrosome regulation and formation of the MITOTIC SPINDLE. Aurora A overexpression in many malignant tumor types suggests that it may be directly involved in NEOPLASTIC CELL TRANSFORMATION.
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
An increased tendency to acquire CHROMOSOME ABERRATIONS when various processes involved in chromosome replication, repair, or segregation are dysfunctional.
A family of multisubunit cytoskeletal motor proteins that use the energy of ATP hydrolysis to power a variety of cellular functions. Dyneins fall into two major classes based upon structural and functional criteria.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
Nocodazole is an antineoplastic agent which exerts its effect by depolymerizing microtubules.
The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of CHROMOSOMES, chromosome pairs, or chromosome fragments. In a normally diploid cell (DIPLOIDY) the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is MONOSOMY (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is TRISOMY (symbol: 2N+1).
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.
The first phase of cell nucleus division, in which the CHROMOSOMES become visible, the CELL NUCLEUS starts to lose its identity, the SPINDLE APPARATUS appears, and the CENTRIOLES migrate toward opposite poles.
The orderly segregation of CHROMOSOMES during MEIOSIS or MITOSIS.
A microtubule-associated mechanical adenosine triphosphatase, that uses the energy of ATP hydrolysis to move organelles along microtubules toward the plus end of the microtubule. The protein is found in squid axoplasm, optic lobes, and in bovine brain. Bovine kinesin is a heterotetramer composed of two heavy (120 kDa) and two light (62 kDa) chains. EC 3.6.1.-.
The process by which the CYTOPLASM of a cell is divided.
Orientation of intracellular structures especially with respect to the apical and basolateral domains of the plasma membrane. Polarized cells must direct proteins from the Golgi apparatus to the appropriate domain since tight junctions prevent proteins from diffusing between the two domains.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
An eph family receptor found widely expressed in embryonic and adult tissues. High levels of EphB2 receptor are observed in growing AXONS and NERVE FIBERS. Several isoforms of the protein exist due to multiple alternative mRNA splicing.
Proteins found in the microtubules.
Statement of the position requirements, qualifications for the position, wage range, and any special conditions expected of the employee.
Those customs and ceremonies pertaining to the dead.
Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.
Large multiprotein complexes that bind the centromeres of the chromosomes to the microtubules of the mitotic spindle during metaphase in the cell cycle.
A unisexual reproduction without the fusion of a male and a female gamete (FERTILIZATION). In parthenogenesis, an individual is formed from an unfertilized OVUM that did not complete MEIOSIS. Parthenogenesis occurs in nature and can be artificially induced.
The phase of cell nucleus division following METAPHASE, in which the CHROMATIDS separate and migrate to opposite poles of the spindle.
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional.
A potent phosphodiesterase inhibitor proposed as an antipsychotic agent.
The membrane system of the CELL NUCLEUS that surrounds the nucleoplasm. It consists of two concentric membranes separated by the perinuclear space. The structures of the envelope where it opens to the cytoplasm are called the nuclear pores (NUCLEAR PORE).
A 50-kDa protein that complexes with CYCLIN-DEPENDENT KINASE 2 in the late G1 phase of the cell cycle.
Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.
The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.
A key regulator of CELL CYCLE progression. It partners with CYCLIN E to regulate entry into S PHASE and also interacts with CYCLIN A to phosphorylate RETINOBLASTOMA PROTEIN. Its activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P27 and CYCLIN-DEPENDENT KINASE INHIBITOR P21.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
Established cell cultures that have the potential to propagate indefinitely.
The fusion of a spermatozoon (SPERMATOZOA) with an OVUM thus resulting in the formation of a ZYGOTE.
Protein analogs and derivatives of the Aequorea victoria green fluorescent protein that emit light (FLUORESCENCE) when excited with ULTRAVIOLET RAYS. They are used in REPORTER GENES in doing GENETIC TECHNIQUES. Numerous mutants have been made to emit other colors or be sensitive to pH.
Proteins obtained from various species of Xenopus. Included here are proteins from the African clawed frog (XENOPUS LAEVIS). Many of these proteins have been the subject of scientific investigations in the area of MORPHOGENESIS and development.
The chromosomal constitution of a cell containing multiples of the normal number of CHROMOSOMES; includes triploidy (symbol: 3N), tetraploidy (symbol: 4N), etc.
A species of nematode that is widely used in biological, biochemical, and genetic studies.
In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.
Proteins from the nematode species CAENORHABDITIS ELEGANS. The proteins from this species are the subject of scientific interest in the area of multicellular organism MORPHOGENESIS.
A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology.
The final phase of cell nucleus division following ANAPHASE, in which two daughter nuclei are formed, the CYTOPLASM completes division, and the CHROMOSOMES lose their distinctness and are transformed into CHROMATIN threads.
A cyclin subtype that has specificity for CDC2 PROTEIN KINASE and CYCLIN-DEPENDENT KINASE 2. It plays a role in progression of the CELL CYCLE through G1/S and G2/M phase transitions.
Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible.
A species of fruit fly much used in genetics because of the large size of its chromosomes.
The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
A type of CELL NUCLEUS division, occurring during maturation of the GERM CELLS. Two successive cell nucleus divisions following a single chromosome duplication (S PHASE) result in daughter cells with half the number of CHROMOSOMES as the parent cells.
An organization of cells into an organ-like structure. Organoids can be generated in culture. They are also found in certain neoplasms.
The fertilized OVUM resulting from the fusion of a male and a female gamete.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Echinoderms having bodies of usually five radially disposed arms coalescing at the center.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
Female germ cells derived from OOGONIA and termed OOCYTES when they enter MEIOSIS. The primary oocytes begin meiosis but are arrested at the diplotene state until OVULATION at PUBERTY to give rise to haploid secondary oocytes or ova (OVUM).

Cell cycle-dependent expression and centrosome localization of a third human aurora/Ipl1-related protein kinase, AIK3. (1/1931)

We earlier isolated cDNAs encoding novel human protein kinases AIK and AIK2 sharing high amino acid sequence identities with Drosophila Aurora and Saccharomyces cerevisiae Ipl1 kinases whose mutations cause abnormal chromosome segregation. In the present study, a third human cDNA (AIK3) highly homologous to aurora/IPL1 was isolated, and the nucleotide sequence was determined. This cDNA encodes 309 amino acids with a predicted molecular mass of 35.9 kDa. C-terminal kinase domain of AIK3 protein shares high amino acid sequence identities with those of Aurora/Ipl1 family protein kinases including human AIK, human AIK2, Xenopus pEg2, Drosophila Aurora, and yeast Ipl1, whereas the N-terminal domain of AIK3 protein shares little homology with any other Aurora/Ipl1 family members. AIK3 gene was assigned to human chromosome 19q13.43, which is a frequently deleted or rearranged region in several tumor tissues, by fluorescence in situ hybridization, somatic cell hybrid panel, and radiation hybrid cell panel. Northern blot analyses revealed that AIK3 expression was limited to testis. The expression levels of AIK3 in several cancer cell lines were elevated severalfold compared with normal fibroblasts. In HeLa cells, the endogenous AIK3 protein level is low in G1/S, accumulates during G2/M, and reduces after mitosis. Immunofluorescence studies using a specific antibody have shown that AIK3 is localized to centrosome during mitosis from anaphase to cytokinesis. These results suggest that AIK3 may play a role(s) in centrosome function at later stages of mitosis.  (+info)

Abnormal spindle protein, Asp, and the integrity of mitotic centrosomal microtubule organizing centers. (2/1931)

The product of the abnormal spindle (asp) gene was found to be an asymmetrically localized component of the centrosome during mitosis, required to focus the poles of the mitotic spindle in vivo. Removing Asp protein function from Drosophila melanogaster embryo extracts, either by mutation or immunodepletion, resulted in loss of their ability to restore microtubule-organizing center activity to salt-stripped centrosome preparations. This was corrected by addition of purified Asp protein. Thus, Asp appears to hold together the microtubule-nucleating gamma-tubulin ring complexes that organize the mitotic centrosome.  (+info)

Influence of centriole behavior on the first spindle formation in zygotes of the brown alga Fucus distichus (Fucales, Phaeophyceae). (3/1931)

The influence of centrioles, derived from the sperm flagellar basal bodies, and the centrosomal material (MTOCs) on spindle formation in the brown alga Fucus distichus (oogamous) was studied by immunofluorescence microscopy using anti-centrin and anti-beta-tubulin antibodies. In contrast to a bipolar spindle, which is formed after normal fertilization, a multipolar spindle was formed in polyspermic zygote. The number of mitotic poles in polyspermic zygotes was double the number of sperm involved in fertilization. As an anti-centrin staining spot (centrioles) was located at these poles, the multipolar spindles in polyspermic zygotes were produced by the supplementary centrioles. When anucleate egg fragments were fertilized, chromosome condensation and mitosis did not occur in the sperm nucleus. Two anti-centrin staining spots could be detected, microtubules (MTs) radiated from nearby, but the mitotic spindle was never produced. When a single sperm fertilized multinucleate eggs (polygyny), abnormal spindles were also observed. In addition to two mitotic poles containing anti-centrin staining spots, extra mitotic poles without anti-centrin staining spots were also formed, and as a result multipolar spindles were formed. When karyogamy was blocked with colchicine, it became clear that the egg nucleus proceeded independently into mitosis accompanying chromosome condensation. A monoastral spindle could be frequently observed, and in rare cases a barrel-shaped spindle was formed. However, when a sperm nucleus was located near an egg nucleus, the two anti-centrin staining spots shifted to the egg nucleus from the sperm nucleus. In this case, a normal spindle was formed, the egg chromosomes arranged at the equator, and the associated MTs elongated from one pole of the egg spindle toward the sperm chromosomes which were scattered. From these results, it became clear that paternal centrioles derived from the sperm have a crucial role in spindle formation in the brown algae, such as they do during animal fertilization. However, paternal centrioles were not adequate for the functional centrosome during spindle formation. We speculated that centrosomal materials from the egg cytoplasm aggregate around the sperm centrioles and are needed for centrosomal activation.  (+info)

Tobacco BY-2 cell-free extracts induce the recovery of microtubule nucleating activity of inactivated mammalian centrosomes. (4/1931)

The structure and the molecular composition of the microtubule-organizing centers in acentriolar higher plant cells remain unknown. We developed an in vitro complementation assay where tobacco BY-2 extracts can restore the microtubule-nucleating activity of urea-inactivated mammalian centrosomes. Our results provide first evidence that soluble microtubule-nucleating factors are present in the plant cytosolic fraction. The implication for microtubule nucleation in higher plants is discussed.  (+info)

Cyclin-dependent kinase control of centrosome duplication. (5/1931)

Centrosomes nucleate microtubules and duplicate once per cell cycle. This duplication and subsequent segregation in mitosis results in maintenance of the one centrosome/cell ratio. Centrosome duplication occurs during the G1/S transition in somatic cells and must be coupled to the events of the nuclear cell cycle; failure to coordinate duplication and mitosis results in abnormal numbers of centrosomes and aberrant mitoses. Using both in vivo and in vitro assays, we show that centrosome duplication in Xenopus laevis embryos requires cyclin/cdk2 kinase activity. Injection of the cdk (cyclin-dependent kinase) inhibitor p21 into one blastomere of a dividing embryo blocks centrosome duplication in that blastomere; the related cdk inhibitor p27 has a similar effect. An in vitro system using Xenopus extracts carries out separation of the paired centrioles within the centrosome. This centriole separation activity is dependent on cyclin/cdk2 activity; depletion of either cdk2 or of the two activating cyclins, cyclin A and cyclin E, eliminates centriole separation activity. In addition, centriole separation is inhibited by the mitotic state, suggesting a mechanism of linking the cell cycle to periodic duplication of the centrosome.  (+info)

GMAP-210, A cis-Golgi network-associated protein, is a minus end microtubule-binding protein. (6/1931)

We report that a peripheral Golgi protein with a molecular mass of 210 kD localized at the cis-Golgi network (Rios, R.M., A.M. Tassin, C. Celati, C. Antony, M.C. Boissier, J.C. Homberg, and M. Bornens. 1994. J. Cell Biol. 125:997-1013) is a microtubule-binding protein that associates in situ with a subpopulation of stable microtubules. Interaction of this protein, now called GMAP-210, for Golgi microtubule-associated protein 210, with microtubules in vitro is direct, tight and nucleotide-independent. Biochemical analysis further suggests that GMAP-210 specifically binds to microtubule ends. The full-length cDNA encoding GMAP-210 predicts a protein of 1, 979 amino acids with a very long central coiled-coil domain. Deletion analyses in vitro show that the COOH terminus of GMAP-210 binds to microtubules whereas the NH2 terminus binds to Golgi membranes. Overexpression of GMAP-210-encoding cDNA induced a dramatic enlargement of the Golgi apparatus and perturbations in the microtubule network. These effects did not occur when a mutant lacking the COOH-terminal domain was expressed. When transfected in fusion with the green fluorescent protein, the NH2-terminal domain associated with the cis-Golgi network whereas the COOH-terminal microtubule-binding domain localized at the centrosome. Altogether these data support the view that GMAP-210 serves to link the cis-Golgi network to the minus ends of centrosome-nucleated microtubules. In addition, this interaction appears essential for ensuring the proper morphology and size of the Golgi apparatus.  (+info)

HP33: hepatocellular carcinoma-enriched 33-kDa protein with similarity to mitochondrial N-acyltransferase but localized in a microtubule-dependent manner at the centrosome. (7/1931)

Using a new subtraction method and chemically induced rat hepatocellular carcinomas, we identified a hepatocellular carcinogenesis and hepatocyte proliferation-related gene designated hp33 that encoded a 33-kDa protein. The predicted protein was similar to the bovine aralkyl N-acyltransferase and arylacetyl N-acyltransferase. HP33 was restrictively expressed in the liver and kidney, and its gene expression was stimulated in the regenerating liver as well as in hepatocellular carcinoma. Interestingly, it was demonstrated in various hepatic cells that HP33 was localized in regions surrounding the centrosome, where mitochondria were not concentrated. Moreover, its centrosomal localization was evident in the interphase but not in the mitotic phase of the cell cycle. The centrosomal localization of HP33 was dependent on microtubules, and ectopically expressed HP33 was seen at centrosomes even in fibroblasts, which do not exhibit a typical staining pattern of HP33. The centrosomal localization of HP33 became invisible by nocodazole treatment, whereas the mitochondrial staining pattern was not affected by it. In vitro cosedimentation experiments using purified microtubules indicated that HP33 bound to MTs directly and that its MT-binding ability was dependent on the C-terminal basic domain of the protein. These results suggest that, different from early predictions based on its primary structure, HP33 has a growth- and carcinogenesis-related function that may be independent of mitochondrial function.  (+info)

Centrosome amplification and a defective G2-M cell cycle checkpoint induce genetic instability in BRCA1 exon 11 isoform-deficient cells. (8/1931)

Germline mutations of the Brca1 tumor suppressor gene predispose women to breast and ovarian cancers. To study mechanisms underlying BRCA1-related tumorigenesis, we derived mouse embryonic fibroblast cells carrying a targeted deletion of exon 11 of the Brca1 gene. We show that the mutant cells maintain an intact G1-S cell cycle checkpoint and proliferate poorly. However, a defective G2-M checkpoint in these cells is accompanied by extensive chromosomal abnormalities. Mutant fibroblasts contain multiple, functional centrosomes, which lead to unequal chromosome segregation, abnormal nuclear division, and aneuploidy. These data uncover an essential role of BRCA1 in maintaining genetic stability through the regulation of centrosome duplication and the G2-M checkpoint and provide a molecular basis for the role of BRCA1 in tumorigenesis.  (+info)

At the onset of mitosis, the centrosome expands and matures, acquiring enhanced activities for microtubule nucleation and assembly of a functional bipolar mitotic spindle. However, the mechanisms that regulate centrosome expansion and maturation are largely unknown. Previously, we demonstrated in an immortalized human cell line CGL2 and cancer cell line HeLa that the inducible form of heat shock protein 70 (HSP70) accumulates at the mitotic centrosome and is required for centrosome maturation and bipolar spindle assembly. In this study, we further show that HSP70 accumulated at the spindle pole in a PLK1-dependent manner. HSP70 colocalized with pericentrin (PCNT), CEP215 and γ-tubulin at the spindle pole and was required for the 3D assembly of these three proteins, which supports mitotic centrosome function. Loss of HSP70 disrupted mitotic centrosome structure, reduced pericentriolar material recruitment and induced fragmentation of spindle poles. In addition, HSP70 was necessary for the interaction
Centrosomes play critical roles in processes that ensure proper segregation of chromosomes and maintain the genetic stability of human cells. They contribute to mitotic spindle organization and regulate aspects of cytokinesis and cell cycle progression. We and others have shown that centrosomes are abnormal in most aggressive carcinomas. Moreover, centrosome defects have been implicated in chromosome instability and loss of cell cycle control in invasive carcinoma. Others have suggested that centrosome defects only occur late in tumorigenesis and may not contribute to early steps of tumor development. To address this issue, we examined pre-invasive human carcinoma in situ lesions for centrosome defects and chromosome instability. We found that a significant fraction of precursor lesions to some of the most common human cancers had centrosome defects, including in situ carcinomas of the uterine cervix, prostate, and female breast. Moreover, centrosome defects occurred together with mitotic spindle
The centrosome is copied only once per cell cycle. Each daughter cell inherits one centrosome, containing two centrioles. The centrosome replicates during the interphase of the cell cycle. During the prophase of mitosis, the centrosomes migrate to opposite poles of the cell. The mitotic spindle then forms between the two centrosomes. Upon division, each daughter cell receives one centrosome. Centrosomes are not needed for the mitosis to happen. When the centrosomes are irradiated by a laser, mitosis proceeds with a normal spindle. In the absence of the centrosome, the microtubules of the spindle are focused to form a bipolar spindle. Many cells can completely undergo interphase without centrosomes.[6] Although centrosomes are not needed for mitosis or the survival of the cell, they are needed for survival of the organism. Cells without centrosomes lack certain microtubules. With centrosomes the cell division is much more accurate and efficient. Some cell types arrest in the following cell cycle ...
Centrosomes are composed of a pair of barrel-shaped, 9-fold symmetric centrioles, surrounded by a proteinaceous matrix collectively referred to as pericentriolar material (PCM).1 Centrosomes are the major microtubule organizing centers in mammalian cells and participate in various cellular processes that include cell motility, mitotic cell division, and ciliogenesis. Proteomic characterization and protein correlation profiling established that the human centrosome is composed of over 100 proteins (1). Understanding how this intricate array of proteins is organized into functionally distinct protein complexes that regulate various aspects of centrosome biogenesis, function, and architecture constitutes a major challenge.. Centrosome biogenesis and function is tightly regulated during the cell cycle. Indeed, the single interphase centrosome must duplicate once and only once during the cell cycle such that two centrosomes are present in mitosis, with each centrosome organizing one pole of the ...
Cells have intrinsic mechanisms that facilitate centrosome clustering (Godinho and Pellman, 2014). Thus, it is thought that cells are unlikely to require adaptation to centrosome amplification, which is further supported by the fact that most cancer cell lines with extra centrosomes are able to cluster centrosomes efficiently (Ring et al., 1982; Quintyne et al., 2005; Kwon et al., 2008; Ganem et al., 2009). However, our findings challenge this idea and indicate that at least in epithelial tumors, cancer cells need to adapt to efficiently proliferate in the presence of supernumerary centrosomes. We demonstrate that induction of centrosome amplification in a panel of nontransformed cell lines reveals intrinsic differences in clustering ability, with epithelial cells displaying an inefficient process. These differences are not caused by centrosome inactivation, as previously shown in Drosophila cells with extra centrosomes (Sabino et al., 2015), highlighting that the prevalence of mechanisms that ...
Centrosome abnormalities are associated with chromosomal instability and defects in cell polarity in tumor cells. For example, human adenocarcinoma cells display a number of abnormalities, including an increase in centrosome number and volume, accumulation of excess pericentriolar matrix, extra centrioles, and aberrant phosphorylation of centrosome-associated proteins, that are believed to contribute to genetic instability and cancer (19 , 30) .. The data presented here implicate centrosomes in neoplastic outgrowth and tumor progression in breast cancer. A well-established carcinogen-induced rat mammary tumor model was applied, and results indicate that centrosome amplification occurred early during tumorigenesis, favoring growth advantage of cells and subsequent neoplastic outgrowth and tumor. Tumors were induced by treating animals with the chemical carcinogen MNU. Tumors appeared several months after treatment, and both early and later stages of tumor development correlated with the presence ...
Centrosome abnormalities are associated with chromosomal instability and defects in cell polarity in tumor cells. For example, human adenocarcinoma cells display a number of abnormalities, including an increase in centrosome number and volume, accumulation of excess pericentriolar matrix, extra centrioles, and aberrant phosphorylation of centrosome-associated proteins, that are believed to contribute to genetic instability and cancer (19 , 30) .. The data presented here implicate centrosomes in neoplastic outgrowth and tumor progression in breast cancer. A well-established carcinogen-induced rat mammary tumor model was applied, and results indicate that centrosome amplification occurred early during tumorigenesis, favoring growth advantage of cells and subsequent neoplastic outgrowth and tumor. Tumors were induced by treating animals with the chemical carcinogen MNU. Tumors appeared several months after treatment, and both early and later stages of tumor development correlated with the presence ...
Centrosome amplification is a hallmark of cancer, and centrosome clustering is essential for cancer cell survival. The mitotic kinesin HSET is an essential contributor to this process. Recent studies have highlighted novel functions for intraflagellar transport (IFT) proteins in regulating motors and mitotic processes. Here, using siRNA knock-down of various IFT proteins or AID-inducible degradation of endogenous IFT88 in combination with small-molecule inhibition of HSET, we show that IFT proteins together with HSET are required for efficient centrosome clustering. We identify a direct interaction between the kinesin HSET and IFT proteins, and we define how IFT proteins contribute to clustering dynamics during mitosis using high-resolution live imaging of centrosomes. Finally, we demonstrate the requirement of IFT88 for efficient centrosome clustering in a variety of cancer cell lines naturally harboring supernumerary centrosomes and its importance for cancer cell proliferation. Overall, our ...
It has become clear that the role of centrosomes extends well beyond that of important microtubule organizers. There is increasing evidence that they also function as coordination centres in eukaryotic cells, at which specific cytoplasmic proteins interact at high concentrations and important cell decisions are made. Accordingly, hundreds of proteins are concentrated at centrosomes, including cell cycle regulators, checkpoint proteins and signalling molecules. Nevertheless, several observations have raised the question of whether centrosomes are essential for many cell processes. Recent findings have shed light on the functions of centrosomes in animal cells and on the molecular mechanisms of centrosome assembly, in particular during mitosis. These advances should ultimately allow the in vitro reconstitution of functional centrosomes from their component proteins to unlock the secrets of these enigmatic organelles.
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Centrosomes nucleate microtubule assembly and determine the number, length, and overall distribution of microtubules within the cell. Consequently, centrosomes influence the position and distribution of many cellular organelles including the nucleus. An animal centrosome typically contains a pair of centrioles formed from nine triplet microtubules arranged in a short cylinder surrounded by an electron-dense amorphous pericentriolar material (Kellogg et al., 1994). Centrosomes nucleate microtubules in a polarized array with their minus ends originating in the pericentriolar material and their fast growing plus ends directed outward. Centrosomes duplicate precisely once each cell cycle, and in mitosis the daughter centrosomes separate to define the poles of the mitotic spindle (for reviews see Kellogg et al., 1994; Balczon, 1996).. Although a number of studies demonstrate that the centrosomes nucleate and organize microtubule arrays, recent findings indicate that the cell maintains other means of ...
The centrosome acts as the major microtubule-organizing center (MTOC) for cytoskeleton maintenance in interphase and mitotic spindle assembly in vertebrate cells. It duplicates only once per cell cycle in a highly spatiotemporally regulated manner. When the cell undergoes mitosis, the duplicated centrosomes separate to define spindle poles and monitor the assembly of the bipolar mitotic spindle for accurate chromosome separation and the maintenance of genomic stability. However, centrosome abnormalities occur frequently and often lead to monopolar or multipolar spindle formation, which results in chromosome instability and possibly tumorigenesis. A number of studies have begun to dissect the role of mitotic kinases, including NIMA-related kinases (Neks), cyclin-dependent kinases (CDKs), Polo-like kinases (Plks) and Aurora kinases, in regulating centrosome duplication, separation and maturation and subsequent mitotic spindle assembly during cell cycle progression. In this Commentary, we review ...
In animal cells, the interphase centrosome reproduces or duplicates only once per cell cycle, thereby ensuring a strictly bipolar mitotic spindle axis (1). Because there is no cell cycle checkpoint that monitors the number of spindle poles (2), uncontrolled duplication of the centrosome can contribute to genomic instability through the formation of multipolar mitotic spindles. Indeed, many human tumor cells, including those lacking the tumor suppresser protein p53 (3), have abnormally high numbers of centrosomes (4).. Studies of sea urchin and Xenopus embryos and clam oocyte lysates have revealed that the centrosome cycle can be regulated solely by cytoplasmic mechanisms (5-8): The repeated duplication of the centrosome proceeds in the complete absence of either a nucleus (7) or protein synthesis (8). In theory, the cyclical rise and fall in the activity of one or more cyclin-dependent kinases (Cdks) could be the cytoplasmic mechanism that coordinates centrosome reproduction with cell cycle ...
When protein synthesis is completely blocked from before fertilization, the sea urchin zygote arrests in first S phase and the paternal centrosome reduplicates multiple times. However, when protein synthesis is blocked starting in prophase of first mitosis, the zygote divides and the blastomeres arrest in a G1-like state. The centrosome inherited from this mitosis duplicates only once in each blastomere for reasons that are not understood. The late G1 rise in cyclin E/cdk2 kinase activity initiates centrosome duplication in mammalian cells and its activity is needed for centrosome duplication in Xenopus egg extracts. Since the half-time for cyclin E turnover is normally approximately 1 h in sea urchin zygotes, the different behaviors of centrosomes during G1 and S phase arrests could be due to differential losses of cyclin E and its associated kinase activities at these two arrest points. To better understand the mechanisms that limit centrosome duplication, we characterize the levels of cyclin E and
Precise control of centrosome number is crucial for bipolar spindle assembly and accurate transmission of genetic material to daughter cells. Failure to properly control centrosome number results in supernumerary centrosomes, which are frequently found in cancer cells. This presents a paradox: durin …
misc{0b0af07c-dbbc-41c9-a11c-90c428663c54, author = {Carrera, Ana and Alvarado-Kristensson, Maria}, issn = {1551-4005}, keyword = {progression,cell cycle,gamma-tubulin,phosphorylation,SadB,centrosomes}, language = {eng}, number = {24}, pages = {4005--4006}, publisher = {Landes Bioscience}, series = {Cell Cycle}, title = {SADB kinases license centrosome replication}, volume = {8}, year = {2009 ...
Centrosomes organize the bipolar mitotic spindle, and centrosomal defects cause chromosome instability. Protein phosphorylation modulates centrosome function, and we provide a comprehensive map of phosphorylation on intact yeast centrosomes (18 proteins). Mass spectrometry was used to identify 297 phosphorylation sites on centrosomes from different cell cycle stages. We observed different modes of phosphoregulation via specific protein kinases, phosphorylation site clustering, and conserved phosphorylated residues. Mutating all eight cyclin-dependent kinase (Cdk)-directed sites within the core component, Spc42, resulted in lethality and reduced centrosomal assembly. Alternatively, mutation of one conserved Cdk site within γ-tubulin (Tub4-S360D) caused mitotic delay and aberrant anaphase spindle elongation. Our work establishes the extent and complexity of this prominent posttranslational modification in centrosome biology and provides specific examples of phosphorylation control in centrosome ...
The centrosome is the paired organelle that organizes microtubules to form the mitotic spindle. The yeast centrosome (called the spindle pole body) is composed of 18 proteins. To help better understand how the centrosome is regulated, Keck et al. made a comprehensive analysis of phosphorylation of the yeast centrosome proteins by mass spectroscopy. Almost 300 sites of phosphorylation were identified, about 100 of which occurred only during mitosis. The results may help point the way for further functional characterization of the more complicated human centrosome, which, with some 100 proteins, is likely to be regulated by a very large set of phosphorylation events.. J. M. Keck, M. H. Jones, C. C. L. Wong, J. Binkley, D. Chen, S. L. Jaspersen, E. P. Holinger, T. Xu, M. Niepel, M. P. Rout, J. Vogel, A. Sidow, J. R. Yates III, M. Winey, A cell cycle phosphoproteome of the yeast centrosome. Science 332, 1557-1561 (2011). [Abstract] [Full Text]. ...
In animal cells, faithful chromosome segregation depends on the assembly of a bipolar spindle driven by the timely separation of the two centrosomes. Here we took advantage of the highly stereotypical cell divisions in Caenorhabditis elegans embryos to identify new regulators of centrosome separation. We find that at the two-cell stage, the somatic AB cell initiates centrosome separation later than the germline P1 cell. This difference is strongly exacerbated by the depletion of the kinesin-13 KLP-7/MCAK, resulting in incomplete centrosome separation at NEBD in AB but not P1. Our genetic and cell biology data indicate that this phenotype depends on cell polarity via the enrichment in AB of the mitotic kinase PLK-1, which itself limits the cortical localization of the dynein-binding NuMA orthologue LIN-5. We postulate that the timely separation of centrosomes is regulated in a cell type-dependent manner. ...
Using GFP to image microtubules in Dictyostelium, we can follow centrosome and microtubule dynamics in interphase cells and monitor the dramatic changes that result from overexpression of the motor domain of cytoplasmic dynein. Our results address a centering mechanism used in interphase cells to control the position of the centrosome and, indirectly, that of the nucleus. The questions are: what is the role of dynein in interphase cells; where is the force‐generating motor located; and how is its activity controlled?. In wild‐type cells, short‐lived pulling forces dominate the movement of centrosomes, which are consistent with a minus‐end‐directed activity of a motor that is anchored to the cell cortex (Figure 5A and B). The rate of centrosome movement (0.4-2.5 μm/s) is consistent with, but does not prove, a cytoplasmic dynein‐mediated mechanism. To single out the contribution of dynein from the actions of other motor proteins, we have overexpressed the 380 kDa dynein motor domain ...
Centrosomin is a 150 kDa centrosomal protein of Drosophila melanogaster. To study the function of Centrosomin in the centrosome, we have recovered mutations that are viable but male and female sterile (cnnmfs). We have shown that these alleles (1, 2, 3, 7, 8 and hk21) induce a maternal effect on early embryogenesis and result in the accumulation of low or undetectable levels of Centrosomin in the centrosomes of cleavage stage embryos. Hemizygous cnn females produce embryos that show dramatic defects in chromosome segregation and spindle organization during the syncytial cleavage divisions. In these embryos the syncytial divisions proceed as far as the twelfth cycle, and embryos fail to cellularize. Aberrant divisions and nuclear fusions occur in the early cycles of the nuclear divisions, and become more prominent at later stages. Giant nuclei are seen in late stage embryos. The spindles that form in mutant embryos exhibit multiple anomalies. There is a high occurrence of apparently linked ...
The Centrosome Biology Group is led by Dr Fanni Gergely. The work in her laboratory focuses on the centrosome, an organelle best known for its role as a major microtubule organising centre. Emerging evidence, however, suggests that the centrosome also acts as a communication hub that spatially concentrates diverse signalling pathways.. While centrosome number and function are strictly regulated within healthy cells, tumours display a multitude of centrosome abnormalities. How such anomalies contribute to tumourigenesis is an important and as yet unresolved question.. In most normal cells the centrosome is composed of a pair of cylindrical structures, the centrioles, which are embedded in an electron-dense amorphous matrix, the pericentriolar material. The latter provides the site for microtubule nucleation and therefore strongly influences microtubule numbers and organisation throughout the cell cycle. Proteomic studies of whole human centrosomes suggest that the organelle contains up to 300 ...
Formation of a bipolar spindle is indispensable for faithful chromosome segregation and cell division. Spindle integrity is largely dependent on the centrosome and the microtubule network. Centrosome protein Cep57 can bundle microtubules in mammalian cells. Its related protein (Cep57R) in Xenopus was characterized as a stabilization factor for microtubule-kinetochore attachment. Here we show that Cep57 is a pericentriolar material (PCM) component. Its interaction with NEDD1 is necessary for the centrosome localization of Cep57. Depletion of Cep57 leads to unaligned chromosomes and a multipolar spindle, which is induced by PCM fragmentation. In the absence of Cep57, centrosome microtubule array assembly activity is weakened, and the spindle length and microtubule density decrease. As a spindle microtubule-binding protein, Cep57 is also responsible for the proper organization of the spindle microtubule and localization of spindle pole focusing proteins. Collectively, these results suggest that ...
The mechanism by which β-cat* expression induces abnormal centrosome structures in cycling cells and promotes centriole amplification in S-phase-arrested cells is not understood. β-Cat*-expressing cells have a normal DNA content determined by FACS analysis (Bahmanyar et al., 2008), and 98% of β-cat*-expressing cells complete cytokinesis (S.B., unpublished results). Thus, β-cat*-induced extra γ-tubulin puncta are not caused by incomplete cytokinesis. As shown in this study, they are also independent of TCF-mediated transcription. One possibility is that increased centriole splitting caused by β-cat* accumulation at centrosomes (Bahmanyar et al., 2008) destabilizes the scaffolding of pericentriolar proteins, which causes dissociation of fragments of pericentriolar material. Indeed β-cat* increases the mobile pool of γ-tubulin at centrosomes, indicating that the dynamics of some components of the pericentriolar material are changed. Abnormal γ-tubulin puncta contain the centriolar marker ...
During early Drosophila oogenesis, one cell from a cyst of 16 germ cells is selected to become the oocyte, and accumulates oocyte-specific proteins and the centrosomes from the other 15 cells. Here we show that the microtubule cytoskeleton and the centrosomes follow the same stepwise restriction to one cell as other oocyte markers. Surprisingly, the centrosomes still localise to one cell after colcemid treatment, and in BicD and egl mutants, which abolish the localisation of all other oocyte markers and the polarisation of the microtubule cytoskeleton. In contrast, the centrosomes fail to migrate in cysts mutant for Dynein heavy chain 64C, which disrupts the fusome. Thus, centrosome migration is independent of the organisation of the microtubule cytoskeleton, and seems to depend instead on the polarity of the fusome.. ...
We report the identification and primary sequence of PCM-1, a 228-kD centrosomal protein that exhibits a distinct cell cycle-dependent association with the centrosome complex. Immunofluorescence microscopy using antibodies against recombinant PCM-1 demonstrated that PCM-1 is tightly associated with the centrosome complex through G1, S, and a portion of G2. However, late in G2, as cells prepare for mitosis, PCM-1 dissociates from the centrosome and then remains dispersed throughout the cell during mitosis before re-associating with the centrosomes in the G1 phase progeny cells. These results demonstrate that the pericentriolar material is a dynamic substance whose composition can fluctuate during the cell cycle. ...
Defects in the centrosome and cilium are associated with a set of human diseases having diverse phenotypes. To further characterize the components that define the function of these organelles we determined the transcriptional profile of multiciliated tracheal epithelial cells. Cultures of mouse tracheal epithelial cells undergoing differentiation in vitro were derived from mice expressing GFP from the ciliated-cell specific FOXJ1 promoter (FOXJ1:GFP). The transcriptional profile of ciliating GFP+ cells from these cultures was defined at an early and a late time point during differentiation and was refined by subtraction of the profile of the non-ciliated GFP- cells. We identified 649 genes upregulated early, when most cells were forming basal bodies, and 73 genes genes upregulated late, when most cells were fully ciliated. Most, but not all, of known centrosome proteins are transcriptionally upregulated early, particularly Plk4, a master regulator of centriole formation. We found that three genes
Centrosome abnormalities and amplification are common characteristics of tumour cells. Aneuploidy and chromosomal instability are highly correlated with the appearance of multiple centrosomes.. ...
Over a century ago, centrosome aberrations were postulated to cause cancer by promoting genome instability. The mechanisms governing centrosome assembly and function are increasingly well understood, allowing for a timely reappraisal of this postulate. This Review discusses recent advances that shed …
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Centrosome-associated protein E (CENPE) is a kinesin-like motor protein that accumulates in the G2 phase of the cell cycle. Unlike other centrosome-associated proteins, it is not present during interphase and first appears at the centromere region of chromosomes during prometaphase. This protein is required for stable spindle microtubule capture at kinetochores which is a necessary step in chromosome alignment during prometaphase. This protein also couples chromosome position to microtubule depolymerizing activity. Alternative splicing results in multiple transcript variants encoding distinct protein isoforms. [provided by RefSeq, Nov 2014 ...
A homozygous truncating frameshift mutation in CEP57 (CEP57T/T) has been identified in a subset of mosaic-variegated aneuploidy (MVA) patients; however, the physiological roles of the centrosome-associated protein CEP57 that contribute to disease are unknown. To investigate these, we have generated a mouse model mimicking this disease mutation. Cep57T/T mice died within 24 hours after birth with short, curly tails and severely impaired vertebral ossification. Osteoblasts in lumbosacral vertebrae of Cep57T/T mice were deficient for Fgf2, a Cep57 binding partner implicated in diverse biological processes, including bone formation. Furthermore, a broad spectrum of tissues of Cep57T/T mice had severe aneuploidy at birth, consistent with the MVA patient phenotype. Cep57T/T mouse embryonic fibroblasts and patient-derived skin fibroblasts failed to undergo centrosome maturation in G2 phase, causing premature centriole disjunction, centrosome amplification, aberrant spindle formation, and high rates of ...
In a new study, Dana-Farber Cancer Institute scientists disprove a century-old theory about why cancer cells often have too many or too few chromosomes, and show that the actual reason may hold the key to a novel approach to cancer therapy.. Since the late 19th century, scientists have attributed the surplus or shortage of intact chromosomes in cancer cells to a kind of fragmentation in cell division: instead of dividing neatly into two identical daughter cells, as normal cells do, cancer cells were thought to frequently split into three or four cells, each with a motley assortment of chromosomes. This explosive division was thought to occur because many cancer cells have extra centrosomes, tiny circular structures that help pairs of chromosomes line up in preparation for cell division.. When study lead author Neil Ganem, PhD, of Dana-Farber used newly developed microscope equipment to watch living cancer cells for a week or more, he found that not only were such abnormal divisions quite rare, ...
Centrosome, besides being a microtubule nucleator, is also important during the cell cycle because it contains many proteins involved in the progress of the cell cycle and in the organization of the mitotic spindle. For example, duplication of centrosomes before mitosis is essential to produce two healthy new cells. In this way, centrosome has been proposed as the cause of different types of cancer since many tumor cells have supernumerary centrosomes that may produce multipolar mitotic spindles and unequal distribution of chromosomes (aneuploidy). There are other cellular places where microtubules can be nucleated. For example, chromosomes during mitosis, cisterns of Golgi apparatus, basal bodies of cilia and flagella, and some new nucleation points sometimes depend on other microtubule. Blepharoplasts (also MTOCs) are molecular complexes of plant cells, occasionally found in animal cells, which are able to nucleate microtubules, and sometimes give rise to centrioles and centrosomes. Plant ...
T cell receptor (TCR)-mediated cytoskeletal reorganization is considered to be actin-related protein (Arp) 2/3 complex dependent. We therefore examined the requirement for Arp2/3- and formin-dependent F-actin nucleation during T cell activation. We demonstrated that without Arp2/3-mediated actin nucleation, stimulated T cells could not form an F-actin-rich lamellipod, but instead produced polarized filopodia-like structures. Moreover, the microtubule-organizing center (MTOC, or centrosome), which rapidly reorients to the immunological synapse through an unknown mechanism, polarized in the absence of Arp2/3. Conversely, the actin-nucleating formins, Diaphanous-1 (DIA1) and Formin-like-1 (FMNL1), did not affect TCR-stimulated F-actin-rich structures, but instead displayed unique patterns of centrosome colocalization and controlled TCR-mediated centrosome polarization. Depletion of FMNL1 or DIA1 in cytotoxic lymphocytes abrogated cell-mediated killing. Altogether, our results have identified Arp2/3 complex
The Bazzi laboratory is investigating the roles of cytoskeletal organizers in mammalian development and homeostasis. Dr. Bazzi and his team are focusing on the functions of centrosomes in the developing mouse and in stem cells. They use mouse genetics to study the consequences of the loss of centrosomes on various cell processes such as cell cycle, division, polarity, migration, signaling and fate determination. The labs goal is to shed light on centrosome-related human diseases and to help find ways of treating them. Our research: The Bazzi laboratory studies centrosome function in stem cells. The team aims to define the function of centrosomes in asymmetric stem cell divisions in the developing and regenerative skin stem cells. To this end, they use mouse genetic approaches in vivo for the conditional removal of the centrosome, and investigate the consequences and the corresponding mechanisms. Our successes: Using genetic mutations in the mouse, the team has removed centrosome function in the ...
Centrosome asymmetry plays a key role in ensuring the asymmetric division of Drosophila neural stem cells (neuroblasts [NBs]) and male germline stem cells (GSCs) [1-3]. In both cases, one centrosome is anchored close to a specific cortical region during interphase, thus defining the orientation of the spindle during the ensuing mitosis. To test whether asymmetric centrosome behavior is a general feature of stem cells, we have studied female GSCs, which divide asymmetrically, producing another GSC and a cystoblast. The cystoblast then divides and matures into an oocyte, a process in which centrosomes exhibit a series of complex behaviors proposed to play a crucial role in oogenesis [4-6]. We show that the interphase centrosome does not define spindle orientation in female GSCs and that DSas-4 mutant GSCs [7], lacking centrioles and centrosomes, invariably divide asymmetrically to produce cystoblasts that proceed normally through oogenesis-remarkably, oocyte specification, microtubule organization, and
Neoplastic cells are genetically unstable. Strategies that target pathways affecting genome instability can be exploited to disrupt tumor cell growth potentially with limited consequences to normal cells. Chromosomal instability (CIN) is one type of genome instability characterized by mitotic defects that increase the rate of chromosome mis-segregation. CIN is frequently caused by extra centrosomes that transiently disrupt normal bipolar spindle geometry needed for accurate chromosome segregation. Tumor cells survive with extra centrosomes because of biochemical pathways that cluster centrosomes and promote chromosome segregation on bipolar spindles. Recent work shows that targeted inhibition of these pathways prevents centrosome clustering and forces chromosomes to segregate to multiple daughter cells, an event triggering apoptosis that we refer to as anaphase catastrophe. Anaphase catastrophe specifically kills tumor cells with more than two centrosomes. This death program can occur after ...
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The bipolar spindle forms without centrosomes naturally in female meiosis and by experimental manipulation in mitosis. Augmin is a recently discovered protein complex required for centrosome-independent microtubule generation within the spindle in Drosophila melanogaster cultured cells. Five subunits of Augmin have been identified so far, but neither their organization within the complex nor their role in developing organisms is known. In this study, we report a new Augmin subunit, wee Augmin component (Wac). Wac directly interacts with another Augmin subunit, Dgt2, via its coiled-coil domain. Wac depletion in cultured cells, especially without functional centrosomes, causes severe defects in spindle assembly. We found that a wac deletion mutant is viable but female sterile and shows only a mild impact on somatic mitosis. Unexpectedly, mutant female meiosis showed robust microtubule assembly of the acentrosomal spindle but frequent chromosome misalignment. For the first time, this study ...
Protein kinase which is involved in the control of centrosome separation and bipolar spindle formation in mitotic cells and chromatin condensation in meiotic cells. Regulates centrosome separation (essential for the formation of bipolar spindles and high-fidelity chromosome separation) by phosphorylating centrosomal proteins such as CROCC, CEP250 and NINL, resulting in their displacement from the centrosomes. Regulates kinetochore microtubule attachment stability in mitosis via phosphorylation of NDC80. Involved in regulation of mitotic checkpoint protein complex via phosphorylation of CDC20 and MAD2L1. Plays an active role in chromatin condensation during the first meiotic division through phosphorylation of HMGA2. Phosphorylates: PPP1CC; SGO1; NECAB3 and NPM1. Essential for localization of MAD2L1 to kinetochore and MAPK1 and NPM1 to the centrosome. Phosphorylates CEP68 and CNTLN directly or indirectly (By similarity). NEK2-mediated phosphorylation of CEP68 promotes CEP68 dissociation from the
Based on its early recruitment to the satellite SPB and its requirement for SPB localization of multiple SPB components, we propose that Ppc89 functions as a platform for assembly of a new SPB (Fig. 7 A). The C terminus of Ppc89 has previously been shown to interact with Sid4 (Rosenberg et al., 2006), and our SPA-SIM data show that this end of Ppc89 extends away from the NE to function in assembly of an outer module that includes Sid4, Cdc11, and Mto1. The N terminus of Ppc89 is located near the C terminus of Pcp1, which would facilitate assembly of a central module, which contains Cam1 in addition to Pcp1 (Fig. 7 B). The idea that Pcp89 connects SPB submodules makes it functionally analogous to Spc42 in budding yeast. Like Ppc89, Spc42 is also the first component recruited to the bridge, and its C and N terminus interact with orthologues of Sid4 (Cnm67) and Pcp1 (Spc110; Muller et al., 2005; Burns et al., 2015). Although SPA-SIM and immuno-EM data suggest that fluorophores on the N terminus of ...
In animal cells, a center of microtubule organization is the centrosome composed of a pair of cylindrical centrioles surrounded by fibrous pericentriolar material. Microtubules are nucleated from γ-tubulin ring structures embedded in the pericentriolar material. Formation of mitotic spindle is preceded by duplication of centrosome during S phase. Before mitosis, both centrosomes increase their microtubule nucleation capacity and form two microtubule asters that are pushed apart from each other by the forces of motor proteins associated at the microtubule surface. Upon nuclear envelope breakdown, formation of spindle apparatus is finalized by binding chromosomal kinetochores to centrosomal microtubules ...
In the present study, we found that the centrosomes in nearly all pancreatic ductal carcinomas displayed structural abnormalities, such as an increase in their number and size, and an irregular distribution. Quantitative analysis demonstrated a significant difference in centrosome number between normal and cancer cells. In addition, double-labeled immunofluorescence analysis of MIA PaCa-2 pancreatic cancer cells suggest that these aberrant centrosomes contribute to the assembly of multipolar spindles, which may result in the improper segregation of chromosomes during mitosis. These results are consistent with previous studies describing centrosome abnormalities in human malignant tumors of the breast, prostate, brain, lung, and colon (10 , 11) . To our knowledge, however, this is the first report to demonstrate centrosome abnormalities in pancreatic carcinoma.. The centrosome plays a key role in the organization of cytoplasmic microtubules, in the determination of cell polarity, and in the ...
Centrosomes have many important functions and comprise a mother and daughter centriole surrounded by Pericentriolar Material (PCM). The mother centriole recruits and organises the PCM and templates the formation of the daughter centriole. It has been reported that several important Drosophila PCM-organising proteins are recruited to centrioles from the cytosol as part of large cytoplasmic S-CAP complexes that contain the centriole protein Sas-4. In a previous paper [1] we showed that one of these proteins, Cnn, and another key PCM-organising protein, Spd-2, are recruited around the mother centriole before spreading outwards to form a scaffold that supports mitotic PCM assembly; the recruitment of Cnn and Spd-2 is dependent on another S-CAP protein, Asl. We show here, however, that Cnn, Spd-2 and Asl are not recruited to the mother centriole as part of a complex with Sas-4. Thus, PCM recruitment in fly embryos does not appear to require cytosolic S-CAP complexes ...
Looking for online definition of centrosome in the Medical Dictionary? centrosome explanation free. What is centrosome? Meaning of centrosome medical term. What does centrosome mean?
Neurons are the signaling cells of the nervous system. To propagate signals, neurons elongate several neurites, which differentiate into a single axon and several dendrites during development. Among the factors that contribute to this differentiation process, the cytoskeleton and in particular the microtubules play a key role. For instance, the growth of the axon and the dendrites depends on dynamic microtubules and requires the formation of new microtubules. The centrosome is regarded as the primary source of microtubules in axonal and dendritic growth and has been proposed to direct axon formation. However, while microtubule nucleation from centrosomes enables efficient spindle-pole organization and cytokinesis during cell division, it is difficult to reconcile the distinct microtubule array in branching axons, dendrites and spines with such focal microtubule assembly. Thus, the exact role of the centrosome and centrosomal microtubule nucleation in axon growth is still unclear. To address this ...
Centrioles are cellular organelles that give rise to the centrosome, a structure composed of a pair of centrioles surrounded by pericentriolar material. Centrosomes perform a variety of different cellular functions: they are the main microtubule organising centre in animal cells and are important
TY - JOUR. T1 - Coordination of centrosome homeostasis and DNA repair is intact in MCF-7 and disrupted in MDA-MB 231 breast cancer cells. AU - Acu, Ilie D.. AU - Liu, Tieju. AU - Suino-Powell, Kelly. AU - Mooney, Steven M.. AU - DAssoro, Antonino B.. AU - Rowland, Nicholas. AU - Muotri, Alysson R.. AU - Correa, Ricardo G.. AU - Niu, Yun. AU - Kumar, Rajiv. AU - Salisbury, Jeffrey L.. N1 - Copyright: Copyright 2010 Elsevier B.V., All rights reserved.. PY - 2010/4/15. Y1 - 2010/4/15. N2 - When cells encounter substantial DNA damage, critical cell cycle events are halted while DNA repair mechanisms are activated to restore genome integrity. Genomic integrity also depends on proper assembly and function of the bipolar mitotic spindle, which is required for equal chromosome segregation. Failure to execute either of these processes leads to genomic instability, aging, and cancer. Here, we show that following DNA damage in the breast cancer cell line MCF-7, the centrosome protein centrin2 moves from ...
Microtubule nucleation requires the γ-tubulin ring complex, and during the M-phase (mitosis) this complex accumulates at the centrosome to support mitotic spindle formation. The posttranslational modification of γ-tubulin through ubiquitination is vital for regulating microtubule nucleation and centrosome duplication. Blocking the BRCA1/BARD1-dependent ubiquitination of γ-tubulin causes centrosome amplification. In the current study, we identified BRCA1-associated protein-1 (BAP1) as a deubiquitination enzyme for γ-tubulin. BAP1 was downregulated in metastatic adenocarcinoma breast cell lines compared with noncancerous human breast epithelial cells. Furthermore, low expression of BAP1 was associated with reduced overall survival of patients with breast cancer. Reduced expression of BAP1 in breast cancer cell lines was associated with mitotic abnormalities. Importantly, rescue experiments including expression of full length but not the catalytic mutant of BAP1 reduced ubiquitination of γ-tubulin and
casSAR Dugability of Q8WXW3 | PIBF1 | Progesterone-induced-blocking factor 1 - Also known as PIBF1_HUMAN, PIBF1, C13orf24, PIBF. Plays a role in ciliogenesis., Pericentriolar protein required to maintain mitotic spindle pole integrity (PubMed:21224392). Required for the centrosomal accumulation of PCM1 and the recruitment of centriolar satellite proteins such as BBS4. Via association with PCM1 may be involved in primary cilia formation (PubMed:23110211). Required for CEP63 centrosomal localization and its interaction with WDR62. Together with CEP63 promotes centriole duplication. Promotes the centrosomal localization of CDK2 (PubMed:26297806)., The secreted form is a mediator of progesterone that by acting on the phospholipase A2 enzyme interferes with arachidonic acid metabolism, induces a Th2 biased immune response, and by controlling decidual naturakl killer cells (NK) activity exerts an anti-abortive effect (PubMed:14634107, PubMed:3863495, PubMed:12516630). Increases the production of Th2-type
Every animal cell has two small organells called centrioles. Centrioles help the cell when it comes time to divide. Mitosis and meiosis both have centrioles involved in. A centriole is a small set of microtubules arranged in a specific way. Also, there are nine groups of microtubles. The centrioles are found in pairs and move towards the poles of the nucleus when it is time for cell division. During interphase, the cell is at rest. The centrioles move to opposite ends of the nucleus and a mitotic spindle of threads begins to appear during prophase. Centrioles are cylindrical structures that composed of groupings of microtubules arranged in 9+3 pattern. They are usually exist in pairs that form centrosomes. Centrioles are found in animal cells and play a big role in cell division. While cell division, the centrosome divides and the centrioles replicate (make new copies). The result is two centrosomes, each with its own pair of centrioles. The two centrosomes move to opposite ends of the nucleus, ...
Duplication of the centrosome is well controlled during faithful cell division while deregulation of this process leads to supernumary centrosomes, chromosome missegregation and aneuploidy, a hallmark of many cancer cells. We previously reported that Polo-like kinase 2 (Plk2) is activated near the G1/S phase transition, and regulates the reproduction of centrosomes. In search for Plk2 interacting proteins we have identified NPM/B23 (Nucleophosmin) as a novel Plk2 binding partner. We find that Plk2 and NPM/B23 interact in vitro in a Polo-box dependent manner. An association between both proteins was also observed in vivo. Moreover, we show that Plk2 phosphorylates NPM/B23 on serine 4 in vivo in S-phase. Notably, expression of a non-phosphorylatable NPM/B23 S4A mutant interferes with centriole reduplication in S-phase arrested cells and leads to a dilution of centriole numbers in unperturbed U2OS cells. The corresponding phospho-mimicking mutants have the opposite effect and their expression leads to the
Centrosomes determine the mitotic axis of dividing control cells asymmetrically. Launch sensory control cells, or neuroblasts (NBs), go through invariant asymmetric cell categories (ACDs). NBs orient their mitotic spindle along a set polarity axis and separate to generate a ganglion mom cell and a self-renewing NB (Kraut et al., 1996). Misalignment of the mitotic spindle network marketing leads to harmful symmetric categories that generate tumors (Cabernard and Doe, 2009). Efficient positioning of the NB mitotic spindle is certainly mediated by centrosomes, which comprise a set of centrioles encircled by pericentriolar materials (PCM) that contains elements required for their microtubule (MT)-arranging middle (MTOC) activity, such as -tubulin (-Tub). The interphase centrosome must copy once in T stage to generate a mom and a little girl centrosome, which after that segregate to distal edges of the cell and older, where the amount of PCM and MTOC activity peak as cells enter mitosis (Khodjakov ...
Mitosis requires extensive rearrangement of cellular architecture and of subcellular buildings in order that replicated chromosomes may bind correctly to spindle microtubules and segregate towards contrary poles. latest advances in understanding the regulation of phosphatase function and activity. Squalamine and embryos, aswell as in individual cultured cells. The system where PP4 promotes the maturation of centrosomes continues to be unidentified, however the phosphatase is apparently necessary for correct centrosomal localization of PLK1 [231] and activation from the the Aurora A-CEP192 complicated [232]. Conversely, disruption of PP4 in MEFs does not have any effect on -tubulin amounts, but qualified prospects to Squalamine unpredictable connections between PCM and microtubules minus-ends [233]. Regulation of microtubule dynamics at the centrosomes and spindle poles relies in part on the activity of the microtubule-severing Katanin complex [234,235], whose centrosomal localization is usually ...
TY - JOUR. T1 - The pericentriolar lattice of PtK2 cells exhibits temperature and calcium-modulated behavior. AU - Baron, Andre T.. AU - Suman, Vera J.. AU - Nemeth, Edward. AU - Salisbury, Jeffrey L.. PY - 1994/11/1. Y1 - 1994/11/1. N2 - In this study, we demonstrate that manipulations of temperature and free calcium alter the morphology of the centrin-containing pericentriolar lattice of PtK2 cells. Immunofluorescence microscopy reveals that low-temperature incubation (4°C) causes anti-centrin-labeled pericentrosomal spots to coalesce in the peripheral cytoplasm, and fuses small spots into larger spots near the cell center. At electron microscopic resolution, well-formed pericentriolar satellites appear around the centrioles in response to incubation at 4°C. Elevated free calcium enhances these low-temperature-dependent effects. The data suggest that pericentrosomal spots correspond to one or more pericentriolar satellites, and that pericentriolar satellites and centrosomal matrix are ...
Current Research and Scholarly Interests I am a cell and molecular biologist by training. During my PhD I worked on the identification of thymidine kinase 1 phosphorylation status during cell cycle progression and its relevance for PET imaging of cell proliferation. In the Stearns lab I was interested in how cells cope with multiple centrosomes and what are the mechanisms ensuring centrosome number homeostasis. In the Sebastiano lab I am studying germ cell differentiation and what are the cell biological effects of de-differentiation. ...
The SSX2IP:WRAP73 complex is proposed to act as regulator of spindle anchoring at the mitotic centrosome. Required for the centrosomal localization of SSX2IP and normal mitotic bipolar spindle morphology (PubMed:26545777). Required for the targeting of centriole satellite proteins to centrosomes such as of PCM1, SSX2IP, CEP290 and PIBF1/CEP90. Required for ciliogenesis and involved in the removal of the CEP97:CCP110 complex from the mother centriole. Involved in ciliary vesicle formation at the mother centriole and required for the docking of vesicles to the basal body during ciliogenesis; may promote docking of RAB8A- and ARL13B-containing vesicles (PubMed:26675238).
CENTRIOLES, in the cytoplasm and basal bodies at the plasma membrane, are conserved microtubule-based organelles essential for cell division and cilium formation (Nigg and Raff 2009). Centrioles are essential for fertilization, development, and animal physiological functions (Nigg and Raff 2009). In the newly fertilized egg (i.e., zygote), a centriole normally functions by recruiting pericentriolar material (PCM) and becoming the primary centrosome (Delattre and Gonczy 2004). This centrosome, in the zygote, acts as a microtubule-organizing center and nucleates the astral microtubules that mediate the migration of the female and male nuclei toward each other (Callaini and Riparbelli 1996).. A centriole forms by one of two pathways. In the duplication pathway, a pre-existing centriole acts as a scaffold to ensure that only a daughter centriole is formed per cell cycle. However, the pre-existing centriole does not appear to impart structural information to the daughter (Rodrigues-Martins et al. ...
casSAR Dugability of B4J3F1 | SAK | Serine/threonine-protein kinase PLK4 - Also known as PLK4_DROGR, SAK. Serine/threonine-protein kinase that plays a central role in centriole duplication. Able to trigger procentriole formation on the surface of the mother centriole cylinder, using mother centriole as a platform, leading to the recruitment of centriole biogenesis proteins such as sas-6. When overexpressed, it is able to induce centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole during S phase. Centrosome amplification following overexpression can initiate tumorigenesis, highlighting the importance of centrosome regulation in cancers (By similarity). Homodimer.
TY - JOUR. T1 - Organization of non-centrosomal microtubules in epithelial cells. AU - Toya, Mika. AU - Takeichi, Masatoshi. PY - 2016/1/1. Y1 - 2016/1/1. N2 - Polarized epithelial cells contain a characteristic array of microtubules in which non-centrosomal microtubules are aligned along the apical-to-basal axis of the cell with their minus ends oriented towards the apical pole. Although this unique orientation of microtubules was discovered in the late 1980s, how this orientation is established remains unresolved partly because of limited information about molecular factors that regulate the minus ends of non-centrosomal microtubules. Recent studies, however, identified novel minus end- associated proteins, revealing mechanisms by which the polarized arrays of microtubules are established in epithelial cells. These studies have also demonstrated the importance of apico-basally orientated microtubules in intra-structural organization of cells. This review focuses on recent progress of our ...
The molecular role of the centrosome in the spindle checkpoint has been debated for some time. Müller et al. have now identified a function for a subset of core centrosomal proteins, namely their involvement in the spindle checkpoint. γ-tubulin ring proteins are functionally and biochemically integrated into checkpoint control, together with two of the major players in this pathway, BubR1 and Cdc20. However, the function of the γ-tubulin ring components was not linked to centrosome integrity, nor did it require localization to this organelle.. H. Müller, M.-L. Fogeron, V. Lehmann, H. Lehrach, B. M. H. Lange, A centrosome-independent role for γ-TuRC proteins in the spindle assembly checkpoint. Science 314, 654-657 (2006). [Abstract] [Full Text]. ...
We are happy to welcome you to the 10th Meeting on Cilia, Flagella and Centrosomes, held from the 10th to the 12th of October 2017 at the Séminaire Le Saint Paul (http://lesaintpaul-hotel.fr/).. The CFC conference is a biennial meeting organized in alternation with the European Cilia meeting to bring together around 80 participants working on the biology of cilia, flagella and centrosomes in France and all over Europe. It is an excellent place for lively exchanges between researchers at all stages of their career, from internationally renowned keynote speakers to early stage students.. http://univ-cotedazur.fr/events/cfc2017. ...
Conventional centrosomes are absent from a female meiotic spindle in many animals. Instead, chromosomes drive spindle assembly, but the molecular mechanism of this acentrosomal spindle formation is not well understood. This study screened female sterile mutations for defects in acentrosomal spindle formation in Drosophila female meiosis. One of them, remnants (rem), disrupted bipolar spindle morphology and chromosome alignment in non-activated oocytes. It was found that rem encodes a conserved subunit of Cdc2 (Cks30A). Since Drosophila oocytes arrest in metaphase I, the defect represents a new Cks function before metaphase-anaphase transition. In addition, it was found that the essential pole components, Msps and D-TACC, are often mislocalized to the equator, which may explain part of the spindle defect. The second cks gene cks85A, in contrast, has an important role in mitosis. In conclusion, this study describes a new pre-anaphase role for a Cks in acentrosomal meiotic spindle formation ...
Centriole is a structure found in eukaryotic animal cells. Plant cells and fungi do no contain centrioles. Centriole is the part of the cell, which acts as the center for producing microtubules, which are the component of cytoskeleton. Cytoskeleton is the skeleton of the cell that provides both shape and structure to a cell. Animal cells contain 2 centrioles, which together form the structure, centrosome. In other words, the centrioles are found within the centrosomes, which is a small region in the cytoplasm near the nucleus. Within the centrosomes, the two centrioles are positioned in such a way that both are perpendicular to each other. Like other structures of a cell, centrioles too perform several important functions. Below here is a brief discussion about the centriole function and structure in the study of biology ...
Centrosomal protein of 55 kDa is a protein that in humans is encoded by the CEP55 gene. CEP55 is a mitotic phosphoprotein that plays a key role in cytokinesis, the final stage of cell division. GRCh38: Ensembl release 89: ENSG00000138180 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000024989 - Ensembl, May 2017 Human PubMed Reference:. Mouse PubMed Reference:. Fabbro M, Zhou BB, Takahashi M, Sarcevic B, Lal P, Graham ME, Gabrielli BG, Robinson PJ, Nigg EA, Ono Y, Khanna KK (Oct 2005). Cdk1/Erk2- and Plk1-dependent phosphorylation of a centrosome protein, Cep55, is required for its recruitment to midbody and cytokinesis. Dev Cell. 9 (4): 477-88. doi:10.1016/j.devcel.2005.09.003. PMID 16198290. Entrez Gene: CEP55 centrosomal protein 55kDa. van der Horst A, Simmons J, Khanna KK (November 2009). Cep55 stabilization is required for normal execution of cytokinesis. Cell Cycle. 8 (22): 3742-9. doi:10.4161/cc.8.22.10047. PMID 19855176. Human CEP55 genome location and CEP55 gene ...
Dynein tethers centrosomes to spindle poles. (a) Cytoplasmic dynein is eluted from spindles by addition of mAb 70.1. Immunofluorescent localization of dynei
PCM assembly is driven in part by PLK-1 (Polo-like Kinase) phosphorylation of SPD-5. In embryos, inhibition of PLK-1 or mutation of four PLK-1 target sites on SPD-5 prevents PCM growth (Woodruff et al., 2015; Wueseke et al., 2016). In vitro, PLK-1 phosphorylation of the same four sites accelerates assembly of SPD-5 into supramolecular scaffolds (Woodruff et al., 2015). To check whether dephosphorylation of these PLK-1 sites is critical for PCM disassembly, we performed a small-scale RNAi screen against known mitotic phosphatases. RNAi-mediated depletion of the PP2A phosphatase LET-92 inhibited PCM disassembly (Fig. S1A; Movie 2). PP2A phosphatase localizes to centrosomes and connects to SPD-5 indirectly through the adapter proteins RSA-1 and RSA-2 (Schlaitz et al., 2007). Depletion of the catalytic subunit LET-92 causes pleiotropic effects such as reduced microtubule stability, mitotic spindle collapse, and increased autophagy, which could indirectly affect PCM disassembly (Lehmann et al., 2017; ...
3.0.CO;2-X. PMID 9506584. Fry AM, Mayor T, Meraldi P, Stierhof YD, Tanaka K, Nigg EA (Aug 1998). C-Nap1, a Novel Centrosomal Coiled-Coil Protein and Candidate Substrate of the Cell Cycle-regulated Protein Kinase Nek2. J Cell Biol. 141 (7): 1563-74. doi:10.1083/jcb.141.7.1563. PMC 2133000 . PMID 9647649. Entrez Gene: CEP250 centrosomal protein 250kDa. Kim K, Lee S, Chang J, Rhee K (December 2008). A novel function of CEP135 as a platform protein of C-NAP1 for its centriolar localization. Exp. Cell Res. 314 (20): 3692-700. doi:10.1016/j.yexcr.2008.09.016. PMID 18851962. Human CEP250 genome location and CEP250 gene details page in the UCSC Genome Browser. Gerhard DS, Wagner L, Feingold EA, et al. (2004). The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC). Genome Res. 14 (10B): 2121-7. doi:10.1101/gr.2596504. PMC 528928 . PMID 15489334. Jin J, Smith FD, Stark C, et al. (2004). Proteomic, functional, and domain-based analysis of in ...
Morgana/CHP-1 is a ubiquitously expressed protein able to inhibit ROCK II kinase activity. We have previously demonstrated that morgana haploinsufficiency leads to multiple centrosomes, genomic instability, and higher susceptibility to tumour development. While a large fraction of human cancers has shown morgana down-regulation, a small subset of tumours was shown to express high morgana levels. Here we demonstrate that high morgana expression in different breast cancer subtypes correlates with high tumour grade, mitosis number, and lymph node positivity. Moreover, morgana overexpression induces transformation in NIH-3T3 cells and strongly protects them from various apoptotic stimuli. From a mechanistic point of view, we demonstrate that morgana causes PTEN destabilization, by inhibiting ROCK activity, hence triggering the PI3K/AKT survival pathway. In turn, morgana down-regulation in breast cancer cells that express high morgana levels increases PTEN expression and leads to sensitization of ...
Functions as an anchor sequestering components of the cAMP-dependent pathway to Golgi and/or centrosomes (By similarity).. Participates in microtubule dynamics, promoting microtubule assembly. Depending upon the cell context, may act at the level of the Golgi apparatus or that of the centrosome (PubMed:25217626, PubMed:27666745, PubMed:28814570, PubMed:29162697). In complex with AKAP9, recruits CAMSAP2 to the Golgi apparatus and tethers non-centrosomal minus-end microtubules to the Golgi, an important step for polarized cell movement (PubMed:27666745, PubMed:28814570). In complex with AKAP9, EB1/MAPRE1 and CDK5RAP2, contributes to microtubules nucleation and extension from the centrosome to the cell periphery, a crucial process for directed cell migration, mitotic spindle orientation and cell-cycle progression (PubMed:29162697). ...
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Author: Müller, Hannah; Genre: Thesis; Title: Proteomic and functional analysis of the Drosophila melanogaster centrosome identifies a novel role in cell cycle control
By Donna Hesterman. A team of researchers in UFs chemical engineering department have taken a novel approach to exploring the inner mechanics of a living animal cell.. Using laser scissors to make a precise microscopic cut, Jun Wu, a doctoral student in chemical engineering, carefully sliced one of the stiff spindly spokes that grow out from a cells architectural hub, the centrosome, to find out how a cell finds its center.. There are really two schools of thought about how microtubules work together to move the centrosome to the center of the cell, explained Richard Dickinson, professor and chair of UFs chemical engineering department, who is the senior author on the research paper. One view is that the spokes, or micro-tubules, push the centrosome toward the center as they grow out from the hub and push against the cells outer membrane. The other view is that the microtubules pull the centrosome into place using tiny molecular motors arranged in a series along the microtubules ...
Most differentiated epithelia contain a specialized organelle called a primary cilium. It consists of a protuberance of the apical plasma membrane that ensheathes a rod-like axoneme, composed of nine MT doublets (34). During the differentiation of epithelial cells, from nonpolarized precursors, major rearrangements occur in the cytoskeleton. First, MT are released from the centrosome and align in a longitudinal manner, with their minus ends captured by proteins such as γ-tubulin and ninein, as part of noncentrosomal MTOC, in the apical compartment of the cell (35,36⇓). Second, the centrosome itself takes up a position between the nucleus and the apical plasma membrane, and the distal end of the mother centriole gives rise to the axoneme of the primary cilium (34). Kidney development constitutes a classic model of mesenchymal-epithelial transformation. In the first-trimester human metanephros, at any single time, there coexists a spectrum of cells from undifferentiated mesenchyme, to ...
Cell Organelles: Golgi body, Ribosome, Lysosomes, Centrosome and Micro bodies | Biology Grade XI, a) Golgi body: It is also known as lipochondria or dictyosome. It arises from ER and is formed by four structures. It lies near cell membrane. Cisternae: They are curved with dilated ends and are parallel to each other.
The numerical and spatial specificity of procentriole assembly has historically led to the notion that the mother centriole has only one unique site or template that can seed the assembly of the new procentriole (see [55] for a thoughtful discussion of the possible meanings for this ambiguous term). In its simplest form, the term template implies a structure that directly patterns the cartwheel structure and the nine triplet microtubules of the procentriole-a rubber stamp in the parlance of Fulton. In Paramecium, there is a plaque next to the parent basal body upon which the barrel of triplet microtubules progressively assembles [56] and in Chlamydomonas, there is a looped fibre at the mother basal body containing nine densely staining foci that later elaborate into triplet microtubules [57] (reviewed in [58]). However, it is uncertain whether these structures are the proposed template on the mother basal body or the early assembly intermediates of daughter basal bodies.. Another possibility ...
Centrosome, 3D. "Centrosome 3D Consortium". Research Lab. "Research of Thomas Mayer". University of Konstanz. Archived from the ... thought to promote spindle assembly by cross-linking and sliding along microtubules creating a separation between centrosomes. ...
She is considered a reference in the field of centrosomes biology and has edited a book about methods to study cilia and ... "Biology of centrosomes and genetic instability". Centre de recherche de l'Institut Curie. Retrieved 2020-04-16. Marthiens, ... With her team she continued investigating the biology of centrosomes and the consequences of genetic instabilities. She has ... "Centrosome Amplification Can Initiate Tumorigenesis in Flies". Cell. 133 (6): 1032-1042. doi:10.1016/j.cell.2008.05.039. ISSN ...
Theodor Boveri: biologist, described Centrosome. Karlheinz Brandenburg: Inventor and audio engineer; father of audio ...
Foot, 1894 The Centrosomes of the Fertilization egg of Allolobophora Foetida. Wood's Holl Mar. Bio. Lab. Lect. Foot, 1896-1897 ... Her lecture was titled "The centrosomes of the fertilized egg of Allolobophora foetida". Ella Strobell joined Foot as her ... Foot, 1896 The Origin of the Cleavage Centrosomes J. Morphol. Foot, 1897 The Cocoons and Eggs of Allolobophora Foetida J. ... Centrosome and Archoplasm. Science. Foot, 1897 Yolk-nucleus and Polar Rings J. Morphol. ...
It is part of the centrosome. Model organisms have been used in the study of NINL function. A conditional knockout mouse line, ... 2003). "Polo-like kinase 1 regulates Nlp, a centrosome protein involved in microtubule nucleation". Dev. Cell. 5 (1): 113-25. ... "Phosphorylation of Nlp by Plk1 negatively regulates its dynein-dynactin-dependent targeting to the centrosome". J. Cell Sci. ...
PARP3 is involved in centrosome regulation. Tankyrase is another ADP-ribose polymerase that is involved in telomere length ...
Centrosome In cell biology, the centrosome is an organelle that serves as the main microtubule organizing center (MTOC) of the ... The centrosome is thought to have evolved only in the metazoan lineage of eukaryotic cells. Fungi and plants lack centrosomes ... Bornens, M.; Azimzadeh, J. (2008). "Origin and Evolution of the Centrosome". Eukaryotic Membranes and Cytoskeleton. Advances in ...
The two centrioles in the centrosome are tied to one another. The mother centriole has radiating appendages at the distal end ... Leidel, S.; Delattre, M.; Cerutti, L.; Baumer, K.; Gönczy, P (2005). "SAS-6 defines a protein family required for centrosome ... Edouard Van Beneden made the first observation of centrosomes (which are composed of two orthogonal centrioles) in 1883. In ... The sperm supplies the centriole that creates the centrosome and microtubule system of the zygote. In flagellates and ciliates ...
2011). "Centrosomes and cilia in human disease". Trends in Genetics. 27 (8): 307-315. doi:10.1016/j.tig.2011.05.004. PMC ... She discovered that the kinase PLK4 regulates the number of centrosomes an organism develops. Her simultaneous studies were on ... Bettencourt-Dias, Mónica (December 2013). "Q&A: Who needs a centrosome?". BMC Biology. 11 (1): 28. doi:10.1186/1741-7007-11-28 ...
Feline vaccination Afonso, PV; Zamborlini, A; Saïb, A; Mahieux, R (14 April 2007). "Centrosome and retroviruses: the dangerous ...
... is required for centrosome cohesion. It decorates fibres emanating from the proximal ends of centrioles. During mitosis, ... CEP68 dissociates from centrosomes. CEP68 and rootletin depend both on each other for centriole association, and both also ... are required for centrosome cohesion". Journal of Cell Science. 120 (Pt 24): 4321-31. doi:10.1242/jcs.020248. PMID 18042621. ... "Proteomic characterization of the human centrosome by protein correlation profiling". Nature. 426 (6966): 570-4. doi:10.1038/ ...
Aurora A associates with centrosomes and is believed to regulate mitotic entry. Aurora B is a member of the chromosomal ... At the pointed ends, known as spindle poles, microtubules are nucleated by the centrosomes in most animal cells. Acentrosomal ... In contrast to the search-and-capture mechanism in which centrosomes largely dictate the organization of the mitotic spindle, ... Indeed, it has also been shown that laser ablation of centrosomes in vertebrate cells inhibits neither spindle assembly nor ...
They are commonly organized by the centrosome. In nine triplet sets (star-shaped), they form the centrioles, and in nine ... resist compression but can also bear tension during mitosis and during the positioning of the centrosome). Intermediate ...
Pelletier, L., & Yamashita, Y. (2012). Centrosome asymmetry and inheritance during animal development. Current Opinion In Cell ...
Li, Q; Hansen D; Killilea A; Joshi H C; Palazzo R E; Balczon R (February 2001). "Kendrin/pericentrin-B, a centrosome protein ... Balczon R, Bao L, Zimmer WE (1994). "PCM-1, A 228-kD centrosome autoantigen with a distinct cell cycle distribution". J. Cell ... These were originally thought to be scattered only around the centrosomes, but further studies proved that PCM1 was also found ... PCM1 forms a complex at the centrosome with disrupted-in-schizophrenia 1 (DISC1) and Bardet-Biedl syndrome 4 protein (BBS4), ...
The globular chains attempt to move towards the centrosome, but as they are bound to the cell membrane, this results in pulling ... At the negative ends of the aster , centrosomes will nucleate (form a nucleus) and anchor to the microtubules. At the positive ... An aster is a cellular structure shaped like a star, consisting of a centrosome and its associated microtubules during the ... They are organized into radial arrays around the centrosomes. The turn-over rate of this population of microtubules is higher ...
PMID:17166055 Bibliography Manandhar G, Schatten H and Sutovsky P (2005). Centrosome reduction during gametogenesis and its ... Manandhar G, Schatten H, Sutovsky P (January 2005). "Centrosome reduction during gametogenesis and its significance". Biol. ... occurs completely without the aid of spindle-coordinating centrosomes. The creation of oogonia traditionally doesn't belong to ...
Hergovich A, Lamla S, Nigg EA, Hemmings BA (2007). "Centrosome-associated NDR kinase regulates centrosome duplication". Mol. ...
"SADB phosphorylation of gamma-tubulin regulates centrosome duplication". Nature Cell Biology. 11 (9): 1081-92. doi:10.1038/ ...
"USP9X regulates centrosome duplication and promotes breast carcinogenesis". Nature Communications. 8: 14866. doi:10.1038/ ...
... when one kinetochore becomes attached to one centrosome, the sister kinetochore becomes exposed to the centrosome located in ... Meraldi P, Lukas J, Fry AM, Bartek J, Nigg EA (June 1999). "Centrosome duplication in mammalian somatic cells requires E2F and ... Mayor T, Meraldi P, Stierhof YD, Nigg EA, Fry AM (June 1999). "Protein kinases in control of the centrosome cycle". FEBS ... In the first place, cells must coordinate centrosome duplication with DNA replication, and a failure in this coordination will ...
Sato, Norihiro (2004). "Radiation Therapy and Centrosome Anomalies in Pancreatic Cancer". In Erich A. Nigg (ed.). Centrosomes ... The multiple centrosomes segregate to opposite ends of the cell and the spindles attach to the chromosomes haphazardly. When ... Spindle formation is mostly conducted by the aster of the centrosome which it forms around itself. In a mitotic cell wherever ... Cells with multipolar spindles are characterized by more than two centrosomes, usually four, and sometimes have a second ...
... has been initially described as a protein to interact with MLLT4 and Actinin, alpha 1. In the context of centrosome ... It has been shown that it functions together with WDR8 in centrosome maturation, ensuring proper spindle length and orientation ... July 2013). "The centriolar satellite protein SSX2IP promotes centrosome maturation". The Journal of Cell Biology. 202 (1): 81- ... "The conserved Wdr8-hMsd1/SSX2IP complex localises to the centrosome and ensures proper spindle length and orientation". ...
2004). "Mammalian RanBP1 regulates centrosome cohesion during mitosis". J. Cell Sci. 116 (Pt 16): 3399-411. doi:10.1242/jcs. ...
The encoded protein localizes to the centrosome where it binds to microtubules as part of a complex referred to as the gamma- ... Hsu LC, White RL (October 1998). "BRCA1 is associated with the centrosome during mitosis". Proceedings of the National Academy ... "Sequential phosphorylation of Nedd1 by Cdk1 and Plk1 is required for targeting of the gammaTuRC to the centrosome". Journal of ... "A direct interaction with NEDD1 regulates gamma-tubulin recruitment to the centrosome". PLOS ONE. 5 (3): e9618. doi:10.1371/ ...
HERC2 has been implicated in regulating stable centrosome architecture in conjunction with NEURL4 other ubiquitinated binding ... Its absence is associated with aberrant centrosome morphology. HERC2 has recently been associated with regulating iron ... "Interaction proteomics identify NEURL4 and the HECT E3 ligase HERC2 as novel modulators of centrosome architecture". Molecular ...
Mi J, Guo C, Brautigan DL, Larner JM (February 2007). "Protein phosphatase-1alpha regulates centrosome splitting through Nek2 ...
2007). "Human Cep192 is required for mitotic centrosome and spindle assembly". Curr. Biol. 17 (22): 1960-6. doi:10.1016/j.cub. ... 2000). "The Centrosomal Protein C-Nap1 Is Required for Cell Cycle-Regulated Centrosome Cohesion". J. Cell Biol. 151 (4): 837-46 ... 2008). "The mammalian SPD-2 ortholog Cep192 regulates centrosome biogenesis". Curr. Biol. 18 (2): 136-41. doi:10.1016/j.cub. ... 2003). "Polo-like kinase 1 regulates Nlp, a centrosome protein involved in microtubule nucleation". Dev. Cell. 5 (1): 113-25. ...
The centrosomes of the species, much like Marchantia polymorpha, are composed of two centrioles apposed end-to end, which are ... Moser, John W. & Kreitner, Gerald L. (February 1, 1970). "Centrosome Structure in Anthoceros Laevis and Marchantia Polymorphia ...
Unlike the centrosome the SPB does not contain centrioles. The SPB organises the microtubule cytoskeleton which plays many ... The spindle pole body (SPB) is the microtubule organizing center in yeast cells, functionally equivalent to the centrosome. ...
See also: Centrosome Cycle.) The centrosome replicates during the S phase of the cell cycle. During the prophase in the process ... The centrosome provides structure for the cell. The centrosome is thought to have evolved only in the metazoan lineage of ... Aberrant numbers of centrosomes in a cell have been associated with cancer. Doubling of a centrosome is similar to DNA ... The centrosome is copied only once per cell cycle, so that each daughter cell inherits one centrosome, containing two ...
These include: centrosome duplication during the G1 phase and S Phase, centrosome maturation in the G2 phase, centrosome ... Initiation of the centrosome cycle occurs early in the cell cycle in order to have two centrosomes by the time mitosis occurs. ... The centrosome cycle is important to ensure that daughter cells receive a centrosome after cell division. As the cell cycle ... Centrosome duplication is heavily regulated by cell cycle controls. This link between the cell cycle and the centrosome cycle ...
Centrosome misorientation reduces stem cell division during ageing. *Jun Cheng1. n5*, Nezaket Türkel2. n5, n6*, Nahid Hemati2. ... J.C. and A.J.H. designed and conducted time-lapse imaging of centrosome behaviour. J.C., N.T., N.H. and Y.M.Y. performed other ... Functionally unequal centrosomes drive spindle orientation in asymmetrically dividing Drosophila neural stem cells. . Dev. Cell ... A role for a novel centrosome cycle in asymmetric cell division. . J. Cell Biol. 177, 13-20 (2007) ...
If centrosomes duplicate more than once within a single cell cycle, centrosome amplification occurs, which is frequently seen ... Upon cytokinesis, each daughter cell receives one centrosome, and thus centrosome must duplicate once, and only once, before ... The presence of more than two centrosomes (centrosome amplification), severely disturbs mitotic process and cytokinesis via ... how loss of certain tumor suppressor proteins leads to centrosome amplification, and the role of centrosome amplification in ...
Centrosomes enlarge dramatically after mitotic entry, when both Aurora A and Polo-like kinases cooperate to recruit additional ... Whereas centrioles are normally duplicated during G1-S phase, PCM components may be loaded onto centrosomes in both a ... Polar expeditions--provisioning the centrosome for mitosis.. Blagden SP1, Glover DM. ...
Make research projects and school reports about Centrosome easy with credible articles from our FREE, online encyclopedia and ... The centrosomes of most animal cells contain a pair of centrioles. During metaphase of mitosis and meiosis, the centrosome ... centrosome In a cell, the distinct part of the cytoplasm that organizes the assembly and disassembly of microtubules and which ... centrosome (centrosphere) (sen-trŏ-sohm) n. an area of clear cytoplasm, found next to the nucleus in nondividing cells, that ...
The yeast centrosome (called the spindle pole body) is composed of 18 proteins. To help better understand how the centrosome is ... Phosphorylation of the yeast centrosome reveals sites of regulation and predicts complex regulation of mammalian centrosomes. ... Phosphorylation of the yeast centrosome reveals sites of regulation and predicts complex regulation of mammalian centrosomes. ... The centrosome is the paired organelle that organizes microtubules to form the mitotic spindle. ...
"Although centrosome defects have been recognized in tumors for a long time," Pellman said, "it has been a tough problem to ... The extra centrosomes in cancer cells exert an unequal pull on some chromosomes, causing the daughter cells to inherit an ... The centrosomes role is to construct the mitotic spindle, the axis along which the chromosome pairs position themselves as ... In normal cells, the two centrosomes serve as the polar ends of the spindle, the chromosomes arrayed between them like ranks of ...
Summary: The centrosome orientation checkpoint acts in Drosophila germline stem cells but not their progeny to ensure oriented ... The centrosome orientation checkpoint is germline stem cell specific and operates prior to the spindle assembly checkpoint in ... Regulation of centrosome movements by Numb and the Collapsin Response Mediator Protein during Drosophila sensory progenitor ... Summary: This Review discusses the multiple roles played by centrosomes during embryonic growth of the vertebrate central ...
The Centrosome: Cell and Molecular Mechanisms of Functions and Dysfunctions in Disease includes chapters on classic and modern ... aspects of centrosome research to cover topics of current interest that h ... download and read The Centrosome ebook online in PDF format for iPhone, iPad, Android, Computer and Mobile readers. Author: ... Centrosomes, DNA Damage and Aneuploidy.- Centrosome Regulation and Breast Cancer.- The Role of Centrosomes in Multiple Myeloma ...
Roles of the centrosome[change , change source]. The centrosome is copied only once per cell cycle. Each daughter cell inherits ... The centrosome replicates during the interphase of the cell cycle. During the prophase of mitosis, the centrosomes migrate to ... Centrosomes are not needed for the mitosis to happen. When the centrosomes are irradiated by a laser, mitosis proceeds with a ... Cells without centrosomes lack certain microtubules. With centrosomes the cell division is much more accurate and efficient. ...
Purchase The Centrosome in Cell Replication and Early Development, Volume 49 - 1st Edition. Print Book & E-Book. ISBN ... Discusses centrosomes and cancer, centrosomes and early development, and molecular biology of the centrosome ... Regulating Centrosomes by Protein Phosphorylation, A.M. Fry, T. Mayor, and E.A. Nigg. The Role of the Centrosome in the ... The Centrosome in Drosophila Oocyte Development, T.L. Megraw and T.C. Kaufman. The Centrosome in Early Drosophila Embryogenesis ...
At each stage, we observed how the remaining proteins are connected to the centriole, the core of the centrosome. We found that ... We then tested how novel proteins affect the protein interaction network of the centrosome. We did this by removing the most ... By being recruited to the centrosome, these older proteins acquired new functions. We thus now have a clearer picture of how ... Here, we study how the evolution of novel proteins helped the formation of the centrosome. Coiled-coil proteins are important ...
... and speculate where the research is headed.Discusses centrosomes and cancer, centrosomes and early development, and molecular ... In addition to the normal growth of cells, centrosomes can also play a key role in the spread of cancer and are of increased ... Volume 49 of Current Topics in Developmental Biology will present all known research surrounding the centrosome, across a ... Centrosomes play an integral role in the growth of cells and the ultimate development of many animals, and sometimes plants. ...
Cells begin to accumulate centrosomes-;organelles that play a vital role during cell division-;before they transform into ... We established a method to identify centrosomes at the single-cell level in clinical samples and found that centrosome number ... The incidence of centrosome amplification increased dramatically during dysplasia, and cells with excess centrosomes persisted ... The researchers never saw excess centrosomes in normal esophageal tissue. Nor did they see centrosome amplification in ...
Left) A field showing the nucleus (N) and a centrosome in the perinuclear area. The two dense bodies (arrows) in the centrosome ... Structural protein 4.1 is located in mammalian centrosomes. Sharon Wald Krauss, Joel Anne Chasis, Catherine Rogers, Narla ... Structural protein 4.1 is located in mammalian centrosomes. Sharon Wald Krauss, Joel Anne Chasis, Catherine Rogers, Narla ... Structural protein 4.1 is located in mammalian centrosomes. Sharon Wald Krauss, Joel Anne Chasis, Catherine Rogers, Narla ...
Centrosomes in development and disease. [Erich A Nigg; John Wiley & Sons.;] -- Discovered over a century ago, the centrosome is ... The centrosome in evolution --. A proteomic approach to the inventory of the human centrosome --. The role of the centrosome in ... The centrosome in evolution -- A proteomic approach to the inventory of the human centrosome -- The role of the centrosome in ... Centrosome regulation in response to environmental and genotoxic stress --. The C. elegans centrosome during early embryonic ...
Connections between the cell cycle, centrosomes and cilia are gaining attention in biomedicine A conference organised by IRB ... The study, published in Nature Cell Biology, focuses on the cell organelle known as centrosome, which organises the network of ...
Centrosome Loss in the Evolution of Planarians. By Juliette Azimzadeh, Mei Lie Wong, Diane Miller Downhour, Alejandro Sánchez ... Centrosome Loss in the Evolution of Planarians. By Juliette Azimzadeh, Mei Lie Wong, Diane Miller Downhour, Alejandro Sánchez ... The centrosome is conserved and essential for the development of all animal species described so far. Here, we show that ... The centrosome, a cytoplasmic organelle formed by cylinder-shaped centrioles surrounded by a microtubule-organizing matrix, is ...
While centrosome fragments are smaller than the fully constituted centrosomes, their microtubule organization function is ... In animal cells, microtubules are organized by centrosomes, which are 1-2 μm diameter organelles. The generation of functional ... The centrosome fragment templates offer greater flexibility and better coverage in both patterning and assembly of microtubules ... and potential for the large-area assembly of microtubules and should expand the application of centrosomes and centrosome ...
USP44 inhibited chromosome segregation errors independent of its role in the mitotic checkpoint by regulating centrosome ...
Anti-gamma Tubulin antibody [GTU-88] - Centrosome Marker (ab11316) Reviews (16) Specific References (114) ... Anti-gamma Tubulin antibody [EPR13872] - Centrosome Marker (ab180595) Reviews (1) Specific References (1) ... Anti-Pericentrin antibody [mAbcam 28144] - Centrosome Marker (ab28144) Reviews (10) Specific References (55) ... Anti-gamma Tubulin antibody - Centrosome Marker (ab16504) Reviews (9) Specific References (21) ...
... Susumu Ohshima ... S. Ohshima and A. Seyama, "Cellular aging and centrosome aberrations," Annals of the New York Academy of Sciences, vol. 1197, ... H. M. J. Hut, W. Lemstra, E. H. Blaauw, G. W. A. Van Cappellen, H. H. Kampinga, and O. C. M. Sibon, "Centrosomes split in the ... O. C. M. Sibon, "Centrosomes as DNA damage regulators," Nature Genetics, vol. 34, no. 1, pp. 6-7, 2003. View at Publisher · ...
... and only later does it become associated with both the old and the new centrosomes.2,3 Centrosomes can initiate microtubule ... During the early phase of the cell cycle, the protein associates predominantly with the old centrosome, ...
... Nature. 2020 Sep;585(7825):447-452. doi: ... Here we show that centrosome depletion induces synthetic lethality in cancer cells that contain the 17q23 amplicon, a recurrent ... In 17q23-amplified cells that lack centrosomes, increased levels of TRIM37 block the formation of foci that comprise ... Finally, we find that the overexpression of TRIM37 causes genomic instability by delaying centrosome maturation and separation ...
... centrosome aberrations causing aneuploidy and genomic instability. Compelling data demonstrate that centrosomes are implicated ... The centrosome is composed of a pair of centrioles surrounded by the pericentriolar material (PMC) and plays a major role in ... Centrosome defects have been found in pre-neoplasias and tumors from breast, ovaries, prostate, head and neck, lung, liver, and ... Hundreds of proteins found in the centrosome exert a variety of roles, including microtubule dynamics, nucleation, and ...
The close physical proximity between the Golgi and the centrosome is a unique feature of mammalian cells that has baffled ... Centrosome abnormalities are emerging hallmarks of cancer. The over-production of centrosomes (known as centrosome ... During interphase, the centrosome nucleates microtubule outgrowth. The centrosome duplicates and, during mitosis, separates to ... An aurora kinase that localizes to the CENTROSOME during MITOSIS and is involved in centrosome regulation and formation of the ...
To test more directly whether the centrosome plays a role in the completion of cytokinesis, we carried out centrosome-removal ... Each centrosome is made up of a daughter centriole that was assembled during the previous S phase and a mother centriole that ... Although centrosome-deprived cells (karyoplasts) have been reported to be unable to enter mitosis (16), this result is at ... 2, B through D). We took advantage of this effect to confirm the role of the centrosome in the control of abscission, as short ...
Centrosomes are autocatalytic droplets of pericentriolar material organized by centrioles. David Zwicker, Markus Decker, ... HSP70 colocalizes with PLK1 at the centrosome and disturbs spindle dynamics in cells arrested in mitosis by arsenic trioxide ... Continuous polo-like kinase 1 activity regulates diffusion to maintain centrosome self-organization during mitosis. Robert ... The role of mitotic kinases in coupling the centrosome cycle with the assembly of the mitotic spindle ...
The centrosome is necessary to initiate axon formation in situ. We next investigated whether or not the centrosome is necessary ... Quantification of the centrosome speed and trajectory. The centrosome velocity was measured using a plugin for ImageJ (Mouse ... Nocodazole (2 μm) increases centrosome motility (red arrowheads, bottom). B, Centrosome velocity changes in cell in A before ... The centrosome velocity was calculated with Excel (Microsoft). The centrosome trajectory was tracked using a plugin for ImageJ ...
  • Although the centrosome has a key role in efficient mitosis in animal cells, it is not essential in certain fly and flatworm species. (wikipedia.org)
  • During mitosis, the nuclear membrane breaks down, and the centrosome-nucleated microtubules can interact with the chromosomes to build the mitotic spindle. (wikipedia.org)
  • During the prophase in the process of cell division called mitosis, the centrosomes migrate to opposite poles of the cell. (wikipedia.org)
  • Initiation of the centrosome cycle occurs early in the cell cycle in order to have two centrosomes by the time mitosis occurs. (wikipedia.org)
  • During mitosis, two centrosomes form spindle poles and direct the formation of bipolar mitotic spindles, which is an essential event for accurate chromosome segregation into daughter cells. (nih.gov)
  • Upon cytokinesis, each daughter cell receives one centrosome, and thus centrosome must duplicate once, and only once, before the next mitosis. (nih.gov)
  • Polar expeditions--provisioning the centrosome for mitosis. (nih.gov)
  • During metaphase of mitosis and meiosis, the centrosome separates into two regions, each containing one of the centrioles (where present). (encyclopedia.com)
  • [4] Although the centrosome has a key role in efficient mitosis in animal cells, it is not necessary. (wikipedia.org)
  • Centrosomes are not needed for the mitosis to happen. (wikipedia.org)
  • When the centrosomes are irradiated by a laser, mitosis proceeds with a normal spindle. (wikipedia.org)
  • Although centrosomes are not needed for mitosis or the survival of the cell, they are needed for survival of the organism . (wikipedia.org)
  • p53 localization at centrosomes during mitosis and postmitotic checkpoint are ATM-dependent and require Serine 15 phosphorylation," Molecular Biology of the Cell , vol. 15, no. 8, pp. 3751-3757, 2004. (hindawi.com)
  • P53 dependent centrosome clustering prevents multipolar mitosis in tetraploid cells," PLoS One , vol. 6, no. 11, Article ID Article numbere27304, 2011. (hindawi.com)
  • The centrosome duplicates and, during mitosis, separates to form the two poles of the mitotic spindle (MITOTIC SPINDLE APPARATUS). (bioportfolio.com)
  • During mitosis, cells possess two centrosomes located at the spindle poles, one of which is inherited by each of the two daughter cells. (sciencemag.org)
  • The centrosome acts as the main microtubule organising center of animal cells and is particularly important during mitosis. (royalsocietypublishing.org)
  • More than a century ago, the German biologist Theodor Boveri observed that cancer cells often had extra centrosomes, organelles essential for the segregation of chromosomes during mitosis. (the-scientist.com)
  • The apicomplexan centrosome has a unique bipartite structure comprising an inner- and outer-core responsible for the nuclear cycle (mitosis) and budding cycles (cytokinesis), respectively. (bioportfolio.com)
  • Abnormal mitosis in a cancer cell containing supernumerary centrosomes. (biologists.com)
  • Furthermore, dynein is necessary initially to position the centrosomes at the nuclear periphery upon entry into mitosis. (biologists.org)
  • Based on these data, the authors propose that dynein, Mud and Asp act sequentially to ensure proper centrosome-spindle coupling during mitosis. (biologists.org)
  • First, NLP ‐induced centrosome aberrations trigger a re‐organization of the cytoskeleton, which stabilizes microtubules and weakens E‐cadherin junctions during mitosis. (embopress.org)
  • Indeed, the single interphase centrosome must duplicate once and only once during the cell cycle such that two centrosomes are present in mitosis, with each centrosome organizing one pole of the bipolar mitotic spindle apparatus ( 2 ). (mcponline.org)
  • It persists throughout mitosis, biasing chromosome segregation in anaphase by causing daughter cells with old centrosomes to retain non-disjoint chromosomes 85% of the time. (elifesciences.org)
  • The centrosome, as a core component of the spindle pole, plays a key role in the establishment of bipolar spindles during mitosis, which is essential for the accurate segregation of chromosomes to daughter cells (reviewed in references 10 and 13 ). (pubmedcentralcanada.ca)
  • hence, the centrosome must duplicate once in each cell cycle prior to the next mitosis. (pubmedcentralcanada.ca)
  • In this context, centrosomes play an essential role in the formation of the microtubule network through which chromosomes move towards opposing poles during mitosis. (healthcanal.com)
  • We demonstrate that TAOK1 and TAOK2 localize to the cytoplasm and centrosomes respectively during mitosis. (aacrjournals.org)
  • The centrosome plays a fundamental role for nucleating and organizing a radial array of cytoplasmic microtubules during interphase and promoting the assembly of the mitotic spindle during mitosis. (epfl.ch)
  • During mitosis, numerous proteins organize protein super-complexes at the three distinct regions of centrosome, kinetochore/centromere and cleavage furrow/midbody. (vifabio.de)
  • In mammalian cells, both the Golgi apparatus and the centrosome play important roles in mitosis. (asm.org)
  • In mitosis, centrosomes organize the mitotic spindle. (aacrjournals.org)
  • Centriole numbers are tightly regulated, and daughter centrioles (which assemble in S phase) cannot themselves duplicate or organize centrosomes until they have passed through mitosis. (ox.ac.uk)
  • These observations can explain why daughter centrioles have to pass through mitosis before they can duplicate and organize a centrosome. (pubmedcentralcanada.ca)
  • We report that GEN1 depletion results in aberrant centrosome numbers associated with the formation of multiple spindle poles in mitosis, an increased number of cells with multi-nuclei, increased apoptosis and an elevated level of spontaneous DNA damage. (ku.dk)
  • Prophase centrosome separation relies on the activity of Eg5/KIF11, a mitotic kinesin [9] that accumulates around centrosomes in early mitosis under the control of CDK1 and the Nek9/Nek6/7 kinase module [10-17]. (deepdyve.com)
  • Our data provide functional evidence that 4.1R makes crucial contributions to the structural integrity of centrosomes and mitotic spindles which normally enable mitosis and anaphase to proceed with the coordinated precision required to avoid pathological events. (asm.org)
  • Herein is reported that in a mouse kidney epithelial cell line, mNek1 localizes to centrosomes in interphase and remains associated with the mitotic spindle pole during mitosis. (asnjournals.org)
  • Researchers previously noted ( 3 , 4 ) that just after mitosis, the centrosome sidles up to the previous-and future-apical crescent of the cell, attaching to the cortex with microtubules. (rupress.org)
  • The encoded protein dissociates from the centrosomes when parental centrioles separate at the beginning of mitosis. (mybiosource.com)
  • However, some CA tumors had low levels of CIN, indicating that protective mechanisms are at play, such as centrosome clustering during mitosis. (biomedcentral.com)
  • during mitosis, centrosomes separate to form poles of the mitotic spindle. (biomedcentral.com)
  • Phosphorylation of the centrosomal protein, Cep169, by Cdk1 promotes its dissociation from centrosomes in mitosis. (semanticscholar.org)
  • Fungi and plants lack centrosomes and therefore use other structures to organize their microtubules. (wikipedia.org)
  • Cells without centrosomes lack radial arrays of astral microtubules. (wikipedia.org)
  • Since the centrosome organizes the microtubules of a cell, it has to do with the formation of the mitotic spindle, polarity and, therefore, cell shape, as well as all other processes having to do with the mitotic spindle. (wikipedia.org)
  • centrosome In a cell , the distinct part of the cytoplasm that organizes the assembly and disassembly of microtubules and which contains the centriole . (encyclopedia.com)
  • The centrosome is the paired organelle that organizes microtubules to form the mitotic spindle. (sciencemag.org)
  • In cell biology , the centrosome is an organelle that is the main place where cell microtubules are organized. (wikipedia.org)
  • In the absence of the centrosome, the microtubules of the spindle are focused to form a bipolar spindle. (wikipedia.org)
  • Cells without centrosomes lack certain microtubules. (wikipedia.org)
  • Making microtubules and mitotic spindles in cells without functional centrosomes. (wikipedia.org)
  • Cells usually contain just a single centrosome that they carefully duplicate once per cell cycle so that, when the cell divides, they can organize microtubules into a bipolar spindle that allows each daughter cell to inherit an equal number of chromosomes and a single centrosome of its own. (news-medical.net)
  • Cell whole mount electron micrograph of microtubules and protein 4.1 at a centrosome of a human fibroblast. (pnas.org)
  • The centrosome controls the number and distribution of microtubules--a major element of the cell cytoskeleton--and hence influences many impo. (worldcat.org)
  • The study, published in Nature Cell Biology , focuses on the cell organelle known as centrosome, which organises the network of microtubules that serves as the cell's skeleton. (irbbarcelona.org)
  • In animal cells, microtubules are organized by centrosomes, which are 1-2 μ m diameter organelles. (ingentaconnect.com)
  • The centrosome fragment templates offer greater flexibility and better coverage in both patterning and assembly of microtubules when compared with intact centrosomes. (ingentaconnect.com)
  • This work provides the rationale and potential for the large-area assembly of microtubules and should expand the application of centrosomes and centrosome components for the creation of microtubule-based nanoscale devices. (ingentaconnect.com)
  • Investigating the behavior of the centrosome in living mitotic cells, we documented a transient and remarkable postanaphase repositioning of this organelle, which apparently controls the release of central microtubules from the midbody and the completion of cell division. (sciencemag.org)
  • Organization of microtubules in centrosome-free cytoplasm. (rupress.org)
  • During interphase, the centrosome organizes an astral array of microtubules (MTs) that participate in fundamental cellular functions such as intracellular trafficking, cell motility, cell adhesion and cell polarity. (scribd.com)
  • Microtubules nucleated from γ-tubulin ring complexes located at the centrosome regulate the localization of organelles, promote vesicular transport and direct cell migration. (biologists.org)
  • Measurement of the density of microtubules close to the centrosome and the rates of GFP-EB1-labeled microtubules emanating from the centrosome indicated that Src signaling promotes microtubule nucleation. (biologists.org)
  • Microtubules are red, centrosomes are green and DNA is blue. (biologists.com)
  • Researchers at the University of California, San Francisco and the Stowers Institute for Medical Research have discovered that planarians, tiny flatworms fabled for their regenerative powers, completely lack centrosomes, cellular structures that organize the network of microtubules that pulls chromosomes apart during cell division. (phys.org)
  • Centrosomes are the main centers for organizing microtubules. (bio-medicine.org)
  • In this study, we show in symmetrically dividing human cells that kinetochore-microtubules associated to old centrosomes are more stable than those associated to young centrosomes, and that this difference favours the accumulation of premature end-on attachments that delay the alignment of polar chromosomes at old centrosomes. (elifesciences.org)
  • Filaments called microtubules assemble from the centrosomes and attach to the chromosomes. (elifesciences.org)
  • The microtubules first align all the chromosomes in the middle of the cell before pulling them towards the centrosomes as the cell divides. (elifesciences.org)
  • The experiments show that the microtubules that assemble from the older centrosome bind the chromosome more tightly than those that form from the younger centrosome. (elifesciences.org)
  • To study the biochemical and structural basis of centrosome-dependent microtubule nucleation, centrosomes capable of organizing microtubules into astral arrays were isolated from parthenogenetically activated Spisula solidissima oocytes. (nih.gov)
  • Jens Januschke and Cayetano González , both scientists at the Institute for Research in Biomedicine (IRB Barcelona), have discovered that microtubules and centrosomes, organelles that govern some cell division processes, participate in memorizing this orientation over successive generations. (healthcanal.com)
  • The centrosome is a cellular component that serves to anchor microtubules, which, like motorways, provide lanes along which various cell components travel. (healthcanal.com)
  • To test the participation of centrosomes in neuroblast orientation, researchers treated cells with colcemide, a drug that decomposes the microtubules of the centrosome and which effect can be reversed. (healthcanal.com)
  • We found that this protein is required for efficient growth of cytoplasmic microtubules from centrosomes as well as for centrosome duplication. (epfl.ch)
  • In animal cells, the centrosome nucleates and anchors microtubules (MT), forming their radial array. (springer.com)
  • Then microtubules and the associated motor and nonmotor proteins anchor the Golgi apparatus in proximity to the centrosome. (asm.org)
  • This pericentriolar localization is thought to be a consequence of the gathering of Golgi vesicles toward the centrosome by minus end-directed motors along microtubules. (asm.org)
  • During interphase, centrosomes organize cytoplasmic microtubules and anchor cilia. (aacrjournals.org)
  • Depletion of HDAC8 caused loss of centrosome-associated microtubules and loss of directed centripetal movement of LEs, dispersing LE/LYs to the cell periphery. (prolekare.cz)
  • Centrosomes nucleate and organize interphase microtubules and are instrumental in mitotic bipolar spindle assembly, ensuring orderly cell cycle progression with accurate chromosome segregation. (asm.org)
  • Centrosomes nucleate and organize interphase microtubules and direct assembly of mitotic bipolar spindles responsible for accurate chromosome segregation in somatic vertebrate cells. (asm.org)
  • Centrosomes consist of a cylindrical tubulin-rich centriole pair, the more mature (or mother) centriole having "appendages" at its distal end appearing to anchor microtubules ( 42 ). (asm.org)
  • The centrosome is more than a hub for microtubules and an anchor for the mitotic spindle. (rupress.org)
  • These scientists proposed that the aster, the starburst of microtubules around the centrosome, retains and transmits neuroblast polarity. (rupress.org)
  • From these results, the researchers conclude that the centrosome remembers a neuroblast's orientation, somehow relaying that information through microtubules. (rupress.org)
  • Centrosomes are composed of two centrioles arranged at right angles to each other, and surrounded by a dense, highly structured mass of protein termed the pericentriolar material (PCM). (wikipedia.org)
  • The centrosome is copied only once per cell cycle, so that each daughter cell inherits one centrosome, containing two structures called centrioles. (wikipedia.org)
  • Unlike centrioles, centrosomes are required for survival of the organism. (wikipedia.org)
  • These centrioles will form the centrosomes, which will direct the first cell division of the zygote, and this will determine its polarity. (wikipedia.org)
  • A centrosome is composed of two orthogonal cylindrical proteins, called centrioles, which are surrounded by an electron and protein dense amorphous cloud of pericentriolar material (PCM). (wikipedia.org)
  • Each daughter cell inherits two centrioles (one centrosome) surrounded by pericentriolar material as a result of cell division. (wikipedia.org)
  • Whereas centrioles are normally duplicated during G1-S phase, PCM components may be loaded onto centrosomes in both a microtubule-dependent and -independent manner at all stages of the cell cycle. (nih.gov)
  • The centrosomes of most animal cells contain a pair of centrioles . (encyclopedia.com)
  • A centrosome is composed of two centrioles at right angles to each another. (wikipedia.org)
  • Each daughter cell inherits one centrosome, containing two centrioles. (wikipedia.org)
  • The two dense bodies (arrows) in the centrosome are a pair of centrioles. (pnas.org)
  • Right ) Two other images of centrosomes heavily decorated with gold beads on centrioles and fibrous structures projecting into the PCM. (pnas.org)
  • The centrosome, a cytoplasmic organelle formed by cylinder-shaped centrioles surrounded by a microtubule-organizing matrix, is a hallmark of animal cells. (sciencemag.org)
  • The centrosome is composed of a pair of centrioles surrounded by the pericentriolar material (PMC) and plays a major role in the regulation of cell cycle transitions (G1-S, G2-M, and metaphase-anaphase), ensuring the normality of cell division. (dovepress.com)
  • 7 In animal cells the centrioles form a cilium in dormant cells, while cells actively cycling form a centrosome. (dovepress.com)
  • 8 Another example is the flatworm Schmidtea mediterranea , which does not regenerate through centrosomes and forms thousands of cilia for motility through the assembly of many centrioles. (dovepress.com)
  • The history of the field, the evolution of the centrosome amongst eukaryotes, the assembly and structure of centrioles, as well as of the surrounding pericentriolar material (PCM) are also covered. (royalsocietypublishing.org)
  • The animal centrosome consists of a pair of centrioles linked together through their proximal regions by a matrix consisting in part of large coiled-coil proteins of the pericentrin family, which anchor other matrix components. (scribd.com)
  • Centrosomes are composed of two centrioles, which are arranged perpendicular to each other and are surrounded by an amorphous mass of proteins known as the pericentriolar material. (phys.org)
  • Complicating matters is the fact centrioles pull double duty: In addition to forming the core of centrosomes, they serve as anchor points for cilia tiny projections on the surface of cells that not only help move fluid and mucus around the brain, lung, eye and kidney and propel eggs down fallopian tubes, but are also essential to sight, smell, mechanosensation and intercellular signaling. (phys.org)
  • The fact that centrioles were retained in this organism while centrosomes were lost, really speaks to the idea that centrioles evolved primarily for making cilia, and not for their mitotic functions. (phys.org)
  • When nuclear division starts, the centrosome divides into two organizing centres which migrate to each pole (along with the CENTRIOLES , if present) and the spindle develops between them. (thefreedictionary.com)
  • Centrosomes are composed of a pair of barrel-shaped, 9-fold symmetric centrioles, surrounded by a proteinaceous matrix collectively referred to as pericentriolar material (PCM). (mcponline.org)
  • NPM/B23 localizes between two centrioles in the unduplicated centrosome. (pubmedcentralcanada.ca)
  • It has been shown that Thr 199 phosphorylation of NPM/B23 is critical for the physical separation of the paired centrioles, an initial event of the centrosome duplication process. (pubmedcentralcanada.ca)
  • The centrosome is composed of a pair of centrioles and surrounding protein aggregates known as pericentriolar material. (pubmedcentralcanada.ca)
  • Centrosome duplication begins with the physical separation of paired centrioles, followed by procentriole formation in the vicinity of each preexisting centriole. (pubmedcentralcanada.ca)
  • Analysis of the centrosomal association of NPM/B23 has revealed that NPM/B23 localizes between the paired centrioles, and upon phosphorylation on Thr 199 by CDK2/cyclin E, the majority of the NPM/B23 proteins dissociate from centrosomes prior to the initiation of centrosome duplication (separation of paired centrioles), implicating NPM/B23 in the pairing of centrioles ( 38 ). (pubmedcentralcanada.ca)
  • C) EM analysis revealed that centrosome fractions contained bona fide centrosomes composed of centrioles (arrows) surrounded by a mass of pericentriolar material ∼2 μm in diameter. (nih.gov)
  • To assess the relative contributions of these two mechanisms, the number of centrosomes with mature/mother centrioles was examined by immunofluorescence in a tissue microarray of human melanomas and benign nevi ( n = 79 and 17, respectively). (aacrjournals.org)
  • Centrosomes, the major microtubule-organizing centers of the cell, are composed of two orthogonal centrioles embedded in a protein-rich pericentriolar material. (aacrjournals.org)
  • Centrioles are cellular organelles that give rise to the centrosome, a structure composed of a pair of centrioles surrounded by pericentriolar material. (ox.ac.uk)
  • Centrioles are small barrel-shaped structures that form centrosomes and cilia [1]. (ox.ac.uk)
  • This creates a Polo-docking site that helps recruit Polo to daughter centrioles and is required for the subsequent recruitment of Asterless (Asl), a protein essential for centriole duplication and mitotic centrosome assembly. (pubmedcentralcanada.ca)
  • Centrioles organize centrosomes and cilia. (pubmedcentralcanada.ca)
  • We report that the multifunctional structural protein 4.1R localizes at centrosomes to distal/subdistal regions of mature centrioles in a cell cycle-dependent pattern. (asm.org)
  • The centrosome consists of a pair of attached centrioles surrounded by proteinaceous pericentriolar material (PCM) and functions as the major microtubule organizing center in human cells [ 1 ]. (biomedcentral.com)
  • Centrosome amplification, chromosome instability and cancer development. (nih.gov)
  • The presence of more than two centrosomes (centrosome amplification), severely disturbs mitotic process and cytokinesis via formation of more than two spindle poles, resulting in an increased frequency of chromosome segregation errors (chromosome instability). (nih.gov)
  • Destabilization of chromosomes by centrosome amplification aids acquisition of further malignant phenotypes, hence promoting tumor progression. (nih.gov)
  • Centrosome amplification occurs frequently in almost all types of cancer, and is considered as the major contributing factor for chromosome instability in cancer cells. (nih.gov)
  • If centrosomes duplicate more than once within a single cell cycle, centrosome amplification occurs, which is frequently seen in cells harboring mutations in some tumor suppressor proteins such as p53 and BRCA1. (nih.gov)
  • In this review, how centrosome amplification destabilizes chromosomes, how loss of certain tumor suppressor proteins leads to centrosome amplification, and the role of centrosome amplification in cancer development will be discussed. (nih.gov)
  • The research, which will be published May 8 in the Journal of Cell Biology , suggests that similar cases of centrosome amplification may contribute to the initiation and progression of a variety of human cancers. (news-medical.net)
  • Centrosome amplification is found in human tumors but not in normal cells, so it is an appealing feature to explore for diagnosis, prognosis, and therapy,' explains Carla Lopes, from the Instituto Português de Oncologia and Instituto Gulbenkian de Ciência in Portugal. (news-medical.net)
  • Lopes and colleagues, including co-first author Marta Mesquita and co-senior authors Mónica Bettencourt-Dias and Paula Chaves, investigated the role of centrosome amplification in tumorigenesis by examining samples from patients with the premalignant condition Barrett's esophagus, in which chronic acid reflux causes the epithelial cells lining the esophagus to be replaced by cells usually found only in the stomach and intestine. (news-medical.net)
  • Nor did they see centrosome amplification in Barrett's esophagus patients that hadn't progressed to later stages of the disease. (news-medical.net)
  • The incidence of centrosome amplification increased dramatically during dysplasia, and cells with excess centrosomes persisted throughout adenocarcinoma and metastasis. (news-medical.net)
  • The increase in centrosome amplification at the onset of dysplasia coincided with the loss or mutation of the tumor suppressor p53. (news-medical.net)
  • Lopes, Mesquita, and colleagues found that p53 was activated in metaplastic cells with extra centrosomes and that removing p53 from these cells increased the levels of centrosome amplification. (news-medical.net)
  • This suggests that centrosome amplification arises in some cells during metaplasia and that p53 prevents these cells from propagating until it is lost during the transition to dysplasia. (news-medical.net)
  • Given the widespread occurrence of p53 mutations and centrosome amplification in human tumors, our findings on the timing and ordering of these events in Barrett's esophagus tumorigenesis are likely applicable to other cancers as well,' Lopes says. (news-medical.net)
  • Centrosome amplification induced by DNA damage occurs during a prolonged G2 phase and involves ATM," EMBO Journal , vol. 23, no. 19, pp. 3864-3873, 2004. (hindawi.com)
  • Induction of centrosome amplification in p53 siRNA-treated human fibroblast cells by radiation exposure," Cancer Science , vol. 97, no. 4, pp. 252-258, 2006. (hindawi.com)
  • Transcriptional control of BubR1 by p53 and suppression of centrosome amplification by BubR1," Molecular and Cellular Biology , vol. 25, no. 10, pp. 4046-4061, 2005. (hindawi.com)
  • Errors in these processes lead to structural (shape, size, number, position, and composition), functional (abnormal microtubule nucleation and disorganized spindles), and numerical (centrosome amplification [CA]) centrosome aberrations causing aneuploidy and genomic instability. (dovepress.com)
  • The over-production of centrosomes (known as centrosome amplification) has been reported in a variety of cancers and is currently being explo. (bioportfolio.com)
  • 14-3-3γ Prevents Centrosome Amplification and Neoplastic Progression. (sigmaaldrich.com)
  • More than 80% of malignant tumors show centrosome amplification and clustering. (sigmaaldrich.com)
  • Centrosome amplification results from aberrations in the centrosome duplication cycle, which is strictly coordinated with DNA-replication-cycle. (sigmaaldrich.com)
  • This report demonstrates that 14-3-3γ localizes to the centrosome and 14-3-3γ loss leads to centrosome amplification. (sigmaaldrich.com)
  • The centrosome amplification led to aneuploidy and increased tumor formation in mice. (sigmaaldrich.com)
  • Recently, the involvement of p53 in CIN through the regulation of centrosome amplification has been proposed in certain tumor types. (nih.gov)
  • In this study, we investigated the relationship between p53 and centrosome amplification in prostate cancer cells. (nih.gov)
  • We provide the first evidence on a correlation between loss of p53 function and centrosome amplification in prostate cancer cells. (nih.gov)
  • Our results indicate that p53 may play a role in the regulation of centrosome amplification and loss of p53 may be one of the mechanisms involving CIN in prostate cancer cells. (nih.gov)
  • Centrosome amplification is sufficient to promote spontaneous tumorigenesis in mammals," Dev Cell , 40:313-22, 2017. (the-scientist.com)
  • Is centrosome amplification a cause or effect of cancer? (the-scientist.com)
  • Still, how much "chromosome segregation errors versus other effects of centrosome amplification [drives tumorigenesis] remains poorly understood. (the-scientist.com)
  • The cells of many solid tumors have been found to contain supernumerary centrosomes, a condition known as centrosome amplification. (aacrjournals.org)
  • Centrosome amplification, accompanied by the overexpression of an associated kinase, Aurora A (AurA), has been implicated in mechanisms leading to mitotic spindle aberrations, aneuploidy, and genomic instability. (aacrjournals.org)
  • Using a well-established rat mammary model favorable for experimental carcinogenesis, we analyzed centrosome amplification as a cellular marker for early stages of transformation and its regulation by the kinase ratAurA . (aacrjournals.org)
  • Parity or treatment with estrogen and progesterone conferred resistance to tumorigenesis, as well as to overexpression of ratAurA and to centrosome amplification. (aacrjournals.org)
  • Centrosome amplification was found to occur at a very early, premalignant stage prior to detectable lesions after treatment with methylnitrosourea, a condition that was not detected in mammary glands of rats made refractory to the carcinogen via pregnancy or estrogen and progesterone treatment. (aacrjournals.org)
  • Cumulatively, these results suggest that ratAurA overexpression and centrosome amplification were linked to tumor development and progression and may serve as early markers in tumorigenesis. (aacrjournals.org)
  • We hypothesize that one of the cellular responses involves a block in carcinogen-induced centrosome amplification. (aacrjournals.org)
  • While tumorigenic effects of centrosome amplification are well‐understood, induction of structural centrosome aberrations by overexpression of ninein‐like protein ( NLP ) reveals an unexpected non‐cell‐autonomous mechanism for dissemination of mitotic cells from epithelia. (embopress.org)
  • Centrosome amplification (CA) is supposed to be one of mechanisms leading to chrosomal instability. (linkos.cz)
  • Immunofluorescent labeling of centrin was used for evaluation of centrosome amplification (CA) in PCs. (linkos.cz)
  • However, it was previously reported that cytokinesis failure does not result in stable centrosome amplification in a cell population ( Krzywicka-Racka and Sluder, 2011 ). (elifesciences.org)
  • To pinpoint the cellular function of RINT-1, we found that RINT-1 depletion by RNA interference led to the loss of the pericentriolar positioning and dispersal of the Golgi apparatus and concurrent centrosome amplification during the interphase. (asm.org)
  • Centrosome amplification (CA) is common in cancer and can arise by centriole overduplication or by cell doubling events, including the failure of cell division and cell-cell fusion. (aacrjournals.org)
  • This study demonstrates that centriole overduplication is the predominant mechanism leading to centrosome amplification in melanoma and that PLK4 should be further evaluated as a potential therapeutic target for melanoma treatment. (aacrjournals.org)
  • Among these, the most common is centrosome amplification (CA), the numerical increase in centrosome number, which has been reported in nearly all human cancers, both solid and hematologic ( 1, 3-8 ), and in some contexts is sufficient for tumorigenesis ( 9 ). (aacrjournals.org)
  • Supplemental Figure 1 - Validation of CEP170 staining in overduplication- versus cell doubling-induced centrosome amplification. (aacrjournals.org)
  • Supplemental Figure 7 - Centrosome amplification does not sensitize to centrinone B. (aacrjournals.org)
  • Complementation of GEN1 depleted cells with various GEN1 constructs revealed that centrosome association but not catalytic activity of GEN1 is required for preventing centrosome hyper-amplification, formation of multiple mitotic spindles, and multi-nucleation. (ku.dk)
  • Centrosome amplification (CA) has been reported in nearly all types of human cancer and is associated with deleterious clinical factors such as higher grade and stage. (biomedcentral.com)
  • Furthermore, structural and functional defects of centrosomes are found in cancer, with the most commonly reported being a numerical excess, known as centrosome amplification (CA) [ 3 ]. (biomedcentral.com)
  • In addition, because centrosomal proteins have a tendency to form aggregates, centrosome-related bodies (CRBs) are often observed in ectopic places. (wikipedia.org)
  • Centrosome maturation is defined as the increase or accumulation of γ-tubulin ring complexes and other PCM proteins at the centrosome. (wikipedia.org)
  • The recent studies have provided critical information for understanding how loss of these proteins allows multiple rounds of centrosome duplication. (nih.gov)
  • Centrosomes enlarge dramatically after mitotic entry, when both Aurora A and Polo-like kinases cooperate to recruit additional gamma-tubulin ring complexes and microtubule-associated proteins to assist spindle formation. (nih.gov)
  • The yeast centrosome (called the spindle pole body) is composed of 18 proteins. (sciencemag.org)
  • made a comprehensive analysis of phosphorylation of the yeast centrosome proteins by mass spectroscopy. (sciencemag.org)
  • The results may help point the way for further functional characterization of the more complicated human centrosome, which, with some 100 proteins, is likely to be regulated by a very large set of phosphorylation events. (sciencemag.org)
  • We identified a large set of conserved proteins required for centriole assembly in animals, and note centrosome protein families that are missing from the planarian genome. (sciencemag.org)
  • Hundreds of proteins found in the centrosome exert a variety of roles, including microtubule dynamics, nucleation, and kinetochore-microtubule attachments that allow correct chromosome alignment and segregation. (dovepress.com)
  • Compelling data demonstrate that centrosomes are implicated in cancer, because there are important oncogenic and tumor suppressor proteins that are localized in this organelle and drive centrosome aberrations. (dovepress.com)
  • Adding a plant hormone spurs the destruction of proteins carrying this segment, and the researchers found that the technique rapidly cut Plk4 levels and blocked centrosome duplication. (rupress.org)
  • Our study provides novel insights into the architecture of human centrosomes and illustrates the power of super-resolution microscopy in revealing the relative localization of centriole and PCM proteins in unprecedented detail. (uniprot.org)
  • Using high resolution imaging, we find that HERC2 and NEURL4 localize to the centrosome and that interfering with their function alters centrosome morphology through the appearance of aberrant filamentous structures that stain for a subset of pericentriolar material proteins including pericentrin and CEP135. (mcponline.org)
  • Proteomic characterization and protein correlation profiling established that the human centrosome is composed of over 100 proteins ( 1 ). (mcponline.org)
  • Understanding how this intricate array of proteins is organized into functionally distinct protein complexes that regulate various aspects of centrosome biogenesis, function, and architecture constitutes a major challenge. (mcponline.org)
  • As part of these pathways, numerous proteins with well‐established non‐centrosomal localization and function associate with the centrosome to fulfill regulatory functions. (embopress.org)
  • Among those, a core group of 11 proteins was critical for centrosome structure maintenance. (embopress.org)
  • Depletion of any of these proteins in Drosophila SL2 cells resulted in centrosome disintegration, revealing a molecular dependency of centrosome structure on components of the protein translation machinery, actin‐ and RNA‐binding proteins. (embopress.org)
  • In total, we assigned novel centrosome‐related functions to 24 proteins and confirmed 13 of these in human cells. (embopress.org)
  • In animal cells, the DNA is arranged within structures called chromosomes and groups of proteins called centrosomes control the process that separates the chromosome copies as the cell divides. (elifesciences.org)
  • 2007) International Worm Meeting "Depletion of lamin and lamin-binding proteins causes a novel centrosome attachment phenotype. (wormbase.org)
  • Our results demonstrate that TAOK inhibition can enhance centrosome declustering and mitotic catastrophe in cancer cells, and these proteins may therefore offer novel therapeutic targets suitable for drug inhibition and the potential treatment of breast cancers, where supernumerary centrosomes occur. (aacrjournals.org)
  • Although many proteins have been identified to be localized on centrosome, kinetochore and/or midbody, an integrated resource on this area still remains not to be available. (vifabio.de)
  • In this work, we have collected all proteins identified to be localized on kinetochore, centrosome, and/or midbody from two fungi (S. cerevisiae and S. pombe) and five animals, including C. elegans, D. melanogaster, X. laevis, M. musculus and H. sapiens. (vifabio.de)
  • From the related literature of PubMed, numerous proteins have been manually curated to be localized on at least one of the sub-cellular localizations of kinetochore, centrosome and midbody. (vifabio.de)
  • The centrosome is composed of hundreds of different proteins, but only a handful are essential. (ox.ac.uk)
  • Significantly, 4.1R-specific depletion mediated by RNA interference perturbs subdistal appendage proteins ninein and outer dense fiber 2/cenexin at mature centrosomes and concomitantly reduces interphase microtubule anchoring and organization. (asm.org)
  • 4.1R depletion causes G 1 accumulation in p53-proficient cells, similar to depletion of many other proteins that compromise centrosome integrity. (asm.org)
  • Immunolocalization of centrosome proteins at the spindle pole. (nih.gov)
  • Aurora-A and CNN are dependent on one another to localize at the spindle pole, and two proteins are required for recruiting γ-tubulin to the centrosome. (nih.gov)
  • Fig. 2 B demonstrates that, besides γ-tubulin, other centrosome proteins, CP190 (a-c) and CP60 (d-f), became dislocated from the spindle poles in RNAi cells. (nih.gov)
  • In flies, Centrosomin (Cnn) forms a phosphorylation-dependent scaffold that recruits proteins to the mitotic centrosome, but how Cnn assembles into a scaffold is unclear. (ox.ac.uk)
  • They report here that loss of Mud results in spindle defects and in displaced or supernumerary centrosomes. (biologists.org)
  • Over 80% of breast cancer tissues display supernumerary centrosomes, and tumor cells frequently cluster extra centrosomes to avoid multipolar mitoses and associated cell death. (aacrjournals.org)
  • The formation of supernumerary centrosomes causes severe problems, since this can lead to multipolar spindle formation, chromosome missegregation and genomic instability, which are hallmarks of cancer cells. (epfl.ch)
  • First, cells with supernumerary centrosomes generate genetic diversity through asymmetric cell divisions on abnormal spindles with chromosome missegregation ( 3, 6, 10 ). (aacrjournals.org)
  • Over a century ago, Theodor Boveri proposed that supernumerary centrosomes can cause cancer [ 4 ]. (biomedcentral.com)
  • CP110 is an important centrosomal protein that is phosphorylated by both mitotic and interphase Cdk/cyclin complexes and is thought to influence centrosome duplication in the S phase. (wikipedia.org)
  • The centrosome replicates during the interphase of the cell cycle. (wikipedia.org)
  • Many cells can completely undergo interphase without centrosomes. (wikipedia.org)
  • During interphase, the centrosome nucleates microtubule outgrowth. (bioportfolio.com)
  • Before a cell divides, the single interphase centrosome duplicates to form the two poles of the mitotic spindle. (ki.se)
  • During interphase centrosome-derived MT, aster can either team up with other MT network or function in an autonomous manner. (springer.com)
  • Burakov A, Kovalenko O, Semenova I, Zhapparova O, Nadezhdina E, Rodionov V (2008a) Cytoplasmic dynein is involved in the retention of MTs at the centrosome in interphase cells. (springer.com)
  • CEP250: Probably plays an important role in centrosome cohesion during interphase. (mybiosource.com)
  • In general, each centriole of the centrosome is based on a nine-triplet microtubule assembled in a cartwheel structure, and contains centrin, cenexin and tektin. (wikipedia.org)
  • In human reproduction, the sperm supplies the centriole that creates the centrosome and microtubule system of the zygote. (wikipedia.org)
  • The centriole is the inner core of the centrosome, and its conformation is typically somewhat like that of spokes on a wheel. (wikipedia.org)
  • Each centrosome is made up of a daughter centriole that was assembled during the previous S phase and a mother centriole that was assembled during a previous cycle. (sciencemag.org)
  • Altogether, the asynchrony of abscission and the correlative movement of the mother centriole to the bridge region suggested the existence of a control that depended on the repositioning of the centrosome. (sciencemag.org)
  • Each daughter cell has inherited a centrosome (CTR1 and CTR2, green arrows) containing a mother centriole (MC1 or MC2) and a daughter centriole (DC1 or DC2). (sciencemag.org)
  • Loss of 14-3-3γ results in the phosphorylation of NPM1 at Thr-199, causing early centriole disjunction and centrosome hyper-duplication. (sigmaaldrich.com)
  • Here, we have used super-resolution 3D-structured illumination microscopy to analyse the spatial relationship of 18 centriole and pericentriolar matrix (PCM) components of human centrosomes at different cell cycle stages. (uniprot.org)
  • 2007). In post-mitotic cells, the centrosome contains a mature centriole called the mother centriole and an immature centriole assembled during the previous cell cycle, the daughter centriole, which is about 80% the length of the mother centriole (Chretien et al. (scribd.com)
  • To determine which centrosome components are required for the assembly and function of its centriole core, Azimzadeh, a postdoctoral researcher in the lab of Marshall, decided to join forces with Sánchez Alvarado and take advantage of planarians' ease of genetic manipulation. (phys.org)
  • Centrosomes are composed of a centriole pair surrounded by an intricate proteinaceous matrix referred to as pericentriolar material. (mcponline.org)
  • Although the mechanisms underpinning the control of centriole duplication are now well understood, we know relatively little about the control of centrosome size and shape. (mcponline.org)
  • The centrosome is an organelle that resides at the center of most animal cells and comprises two microtubule-based centriole cylinders surrounded by pericentriolar material (PCM). (epfl.ch)
  • In proliferating cells, the centrosome duplicates once per cell cycle, a process that involves notably the formation of one procentriole at the base of each centriole. (epfl.ch)
  • Overall, we gained important insights into the functions of CPAP at the centrosome and identified a novel control mechanism of centriole length. (epfl.ch)
  • Depletion of HDAC8 caused centrosome splitting, which could also be induced by depleting a centriole-linker protein, rootletin. (prolekare.cz)
  • Centrosomes and cilia are organized by a centriole pair comprising an older mother and a younger daughter. (ox.ac.uk)
  • Much attention has focused on the mechanisms that regulate centriole (and so centrosome and cilium) numbers, as numerical abnormalities can be highly deleterious to cells. (pubmedcentralcanada.ca)
  • Recently, it was shown in Chlamydomonas that the mature centriole can position the daughter centriole and orient the nucleus ( 11 ) and that in Drosophila asymmetric cell division, the mature centrosome is always inherited by the stem cell ( 68 ). (asm.org)
  • During G 1 , the centrosome contains a mature mother and an immature daughter centriole. (asm.org)
  • It extends on previous topics and includes new exciting aspects of centrosome research focused on primary cilia and their dysfunctions that are implicated in numerous diseases. (ebooks.com)
  • We are pleased to announce the Cold Spring Harbor Asia conference on Cilia & Centrosomes which will be held in Suzhou, China, located approximately 60 miles west of Shanghai. (csh-asia.org)
  • The conference will include eight oral sessions and one poster session covering the latest findings across many topics in Cilia & Centrosomes. (csh-asia.org)
  • When she shut down two planarian homologues of genes known to be required for centrosome assembly in other species, she found that the formation of cilia was perturbed. (phys.org)
  • That's why a Florida State University College of Medicine researcher has been awarded a $1.2 million grant to explore the role of centrosomes and cilia in cell division and development and their connections to human disease. (bio-medicine.org)
  • In recent years proteomic analyses, functional screening, and genome sequencing have not only identified the parts lists of important cellular structures of the microtubule cytoskeleton, such as centrosomes and cilia, but has also revealed their involvement in cancer, their connection to central regulators of cell cycle and cell fate, and their involvement in preventing a range of developmental and degenerative disorders. (irbbarcelona.org)
  • This meeting will gather leaders in related field​s to discuss the latest advances in understanding how the components of centrosomes and cilia are related to cellular function, connected to nuclear signal transduction processes that control genome integrity and how this information can be used to unravel the molecular basis of​complex hereditary disease​s. (irbbarcelona.org)
  • The BARCELONA BIOMED CONFERENCE on Centrosomes, cilia and cell cycle in development and disease will be hosted by the Institut d'Estudis Catalans (IEC) in the heart of downtown Barcelona. (irbbarcelona.org)
  • We have derived an online tool, from a systematic network-based approach to dissect the cilia/centrosome complex interactome (CCCI). (biomedcentral.com)
  • Treatment with the GSK-3β kinase inhibitor also resulted in the loss of the centrosome-derived MT aster, dispersion of PCM-1 over the cytoplasm, and reduction of primary cilia occurrence. (springer.com)
  • Thus, kinases involved in the centrosome-derived MT aster regulation can indirectly control the formation of primary cilia in cells. (springer.com)
  • Taken together with the phenotypes of the mutant mice, these data suggest that mNek1 and mNek8 provide links between cilia, centrosomes, and cell-cycle regulation. (asnjournals.org)
  • Regulating Centrosomes by Protein Phosphorylation, A.M. Fry, T. Mayor, and E.A. Nigg . (elsevier.com)
  • Immunofluorescent localization of protein 4.1 epitopes in centrosomes. (pnas.org)
  • In cell whole mounts of human fibroblasts, protein 4.1 epitopes (5-nm gold beads) and 5051 epitopes (10-nm gold beads) decorated fibrous structures in the centrosome region. (pnas.org)
  • During the early phase of the cell cycle, the protein associates predominantly with the old centrosome, and only later does it become associated with both the old and the new centrosomes. (sigmaaldrich.com)
  • 2,3 Centrosomes can initiate microtubule assembly irrespective of ε-tubulin content, indicating that this protein is not involved in microtubule nucleation. (sigmaaldrich.com)
  • We further show that downregulation of the centrosomal protein Cep120 impairs microtubule organization, resulting in increased centrosome motility. (jneurosci.org)
  • They outfitted Polo-like kinase 4 (Plk4), a protein that controls centrosome duplication, with a segment known as a degron. (rupress.org)
  • As an initial test of this idea, we examined malignant tumors for centrosome abnormalities using antibodies to the centrosome protein pericentrin. (aacrjournals.org)
  • Your search returned 20 ALMS1, centrosome and basal body associated protein ELISA ELISA Kit across 4 suppliers. (biocompare.com)
  • Katanin, a microtubule-severing protein, is a novel AAA ATPase that targets to the centrosome using a WD40-containing subunit. (thefreedictionary.com)
  • Here, we studied the impact of structural centrosome aberrations, induced by deregulated expression of ninein‐like protein ( NLP ), on epithelial spheres grown in Matrigel matrices. (embopress.org)
  • This differential microtubule stability depends on cenexin, a protein enriched on old centrosomes. (elifesciences.org)
  • A protein called cenexin is present at higher levels around older centrosomes than around younger ones and is responsible for this effect. (elifesciences.org)
  • Here, we identified ROCK II kinase, an effector of Rho small GTPase, as a protein that localizes to centrosomes and physically interacts with NPM/B23. (pubmedcentralcanada.ca)
  • RNAi-mediated depletion of CP110 indicates that this protein plays an essential role in centrosome duplication. (thebiogrid.org)
  • They are transported to the centrosome along MTs by the motor protein dynein in a complex with its cofactor dynactin. (springer.com)
  • Here, we show that the RAD50-interacting protein, RINT-1, is localized at the Golgi apparatus and the centrosome in addition to the endoplasmic reticulum. (asm.org)
  • In the present study we demonstrate that GEN1 is a novel centrosome associated protein and we characterize the various phenotypes associated with GEN1 deficiency. (ku.dk)
  • Here, we show that Eg5 localization and centrosome separation in prophase depend on the nuclear microtubule-associated protein TPX2 [18], a pool of which localizes to the centrosomes before NEBD. (deepdyve.com)
  • MBS7251685 is a ready-to-use microwell, strip plate ELISA (enzyme-linked immunosorbent assay) Kit for analyzing the presence of the Centrosome-associated protein CEP250 (CEP250) ELISA Kit target analytes in biological samples. (mybiosource.com)
  • The protein associates with and is phosphorylated by NIMA-related kinase 2, which is also associated with the centrosome. (mybiosource.com)
  • These include: centrosome duplication during the G1 phase and S Phase, centrosome maturation in the G2 phase, centrosome separation in the mitotic phase, and centrosome disorientation in the late mitotic phase-G1 phase. (wikipedia.org)
  • Cell cycle regulation of centrosome duplication Centrosomes are only supposed to replicate once in each cell cycle and are therefore highly regulated. (wikipedia.org)
  • Centrosome duplication is heavily regulated by cell cycle controls. (wikipedia.org)
  • There has been ample evidence that Cdk2 is necessary for both DNA replication and centrosome duplication, which are both key events in S phase. (wikipedia.org)
  • It has also been shown that Cdk2 complexes with both cyclin A and cyclin E and this complex is critical for centrosome duplication. (wikipedia.org)
  • Our findings uncover the molecular basis of regulation of centrosome duplication by 14-3-3γ and inhibition of tumor growth by premature activation of the mitotic program and the disruption of centrosome clustering. (sigmaaldrich.com)
  • Cancer or developmental defects can stem from mistakes in duplication that result in cells carrying an incorrect number of centrosomes. (rupress.org)
  • A canonical duplication cycle generates two centrosomes from one in most proliferating cells. (epfl.ch)
  • Cdk2 activity probably couples centrosome duplication with the S phase, and a licensing mechanism appears to limit centrosome duplication to once per cell cycle. (epfl.ch)
  • However, such mechanisms must be altered in some cells--for example, spermatocytes--in which centrosome duplication and DNA replication are uncoupled. (epfl.ch)
  • This duplication is semi-conservative and results in two centrosomes (mother and daughter) that differ in age, composition and structure. (ki.se)
  • Structure and function of Spc42 coiled-coils in yeast centrosome assembly and duplication. (bioportfolio.com)
  • However, the mechanisms governing centrosome duplication and the underlying structural principles remained poorly understood and represent a long-lasting important question in biology. (nig.ac.jp)
  • Regulation of centrosome structure, duplication and segregation is integrated into cellular pathways that control cell cycle progression and growth. (embopress.org)
  • Nucleophosmin (NPM)/B23 has been implicated in the regulation of centrosome duplication. (pubmedcentralcanada.ca)
  • Expression of the constitutively active form of ROCK II promotes centrosome duplication, while down-regulation of ROCK II expression results in the suppression of centrosome duplication, especially delaying the initiation of centrosome duplication during the cell cycle. (pubmedcentralcanada.ca)
  • Moreover, ROCK II regulates centrosome duplication in its kinase and centrosome localization activity-dependent manner. (pubmedcentralcanada.ca)
  • All these findings point to ROCK II as the effector of the CDK2/cyclin E-NPM/B23 pathway in the regulation of centrosome duplication. (pubmedcentralcanada.ca)
  • In animal cells, centrosome duplication proceeds in coordination with other cell cycle events (i.e. (pubmedcentralcanada.ca)
  • centrosome duplication begins near the G 1 /S boundary and is completed at late G 2 . (pubmedcentralcanada.ca)
  • Initiation of centrosome duplication is triggered by cyclin-dependent kinase 2 (CDK2)/cyclin E (reviewed in reference 18 ), which is activated in late G 1 primarily by temporal expression of cyclin E (reviewed in references 28 and 35 ). (pubmedcentralcanada.ca)
  • Several targets of CDK2 in the initiation of centrosome duplication have been identified, including nucleophosmin (NPM)/B23, Mps1, and CP110 ( 7 , 12 , 32 ). (pubmedcentralcanada.ca)
  • Our data further show that estrogens, interacting with the estrogen receptor α, elicit persistent Aurora A kinase over expression that may affect abnormal centrosome duplication, and together with the loss of p53wt activity by the over expression of MDM2 lead to estrogen-induced oncogenesis. (ku.edu)
  • CP110, a cell cycle-dependent CDK substrate, regulates centrosome duplication in human cells. (thebiogrid.org)
  • Centrosome duplication and separation are linked inextricably to certain cell cycle events, in particular activation of cyclin-dependent kinases (CDKs). (thebiogrid.org)
  • Its expression is strongly induced at the G1-to-S phase transition, coincident with the initiation of centrosome duplication. (thebiogrid.org)
  • Our data suggest that CP110 is a physiological centrosomal CDK target that promotes centrosome duplication, and its deregulation may contribute to genomic instability. (thebiogrid.org)
  • Most of these events result in the concomitant acquisition of extra centrosomes along with genome duplication. (elifesciences.org)
  • The mechanisms regulating centrosome duplication are still incompletely understood. (epfl.ch)
  • 2000) The human papillomavirus type 16 E6 and E7 oncoproteins cooperate to induce mitotic defects and genomic instability by uncoupling centrosome duplication from the cell division cycle. (springer.com)
  • It has recently been shown that centrosome duplication in vertebrates requires Cdk2 activity and can be driven solely by Cdk2-cyclin E complexes. (elsevier.com)
  • For instance, if polyploidy correlates with CA, this would support genome doubling over centrosome duplication or PCM fragmentation. (biomedcentral.com)
  • Moreover, PCM fragmentation is distinguished from duplication in that it is predicted to cause acentriolar centrosomes. (biomedcentral.com)
  • Decreased centrosome motility resulting from microtubule stabilization causes an aberrant centrosomal localization, leading to misplaced axonal outgrowth. (jneurosci.org)
  • Using immunofluorescence analysis with an antibody to γ-tubulin (a well-characterized centrosomal component), we examined surgically resected human pancreatic tissues for centrosome abnormalities. (aacrjournals.org)
  • Furthermore, recovery of GFP-γ-tubulin at the centrosome following photobleaching and measurements of endogenous γ-tubulin levels at the centrosome showed that androgen and Src signaling regulate the levels of centrosomal γ-tubulin. (biologists.org)
  • Upon phosphorylation on Thr 199 by cyclin-dependent kinase 2 (CDK2)/cyclin E, the majority of centrosomal NPM/B23 dissociates from centrosomes, but some NPM/B23 phosphorylated on Thr 199 remains at centrosomes. (pubmedcentralcanada.ca)
  • In this study, we show that a lack of MCPH1 or PCNT results in a loss of Chk1 from centrosomes with subsequently deregulated activation of centrosomal cyclin B-Cdk1. (uzh.ch)
  • The pool of centrosomal TPX2 in prophase has a critical role for both microtubule aster organization and Eg5 localization, and thereby for centrosome separation. (deepdyve.com)
  • Aurora-A and CNN are mutually dependent for localization at spindle poles, which is required for proper targeting of gamma-tubulin and other centrosomal components to the centrosome. (nih.gov)
  • In Mock-transfected control cells, 92% of GFP-Rabin8 expressing cells showed GFP-Rabin8 at the centrosome whereas only 60% of the GFP-Rabin8 expressing TRAPPC8-depleted cells showed centrosomal GFP-Rabin8 localization (50 cells analyzed per condition). (biomedcentral.com)
  • This explosive division was thought to occur because many cancer cells have extra centrosomes, tiny circular structures that help pairs of chromosomes line up in preparation for cell division. (redorbit.com)
  • The way that extra centrosomes do cause chromosome instability, Ganem and his colleagues have discovered, is by setting up a tug-of-war for chromosomes that are eventually caught between newly forming daughter cells of a dividing cancer cell. (redorbit.com)
  • The extra centrosomes in cancer cells exert an unequal pull on some chromosomes, causing the daughter cells to inherit an irregular number of them "" explaining, in part, why tumors are often filled with cells of varying quantities of chromosomes. (redorbit.com)
  • Neil and Susana have made a significant advance by developing useful methods to create comparable cells that carry or don't carry extra centrosomes. (redorbit.com)
  • But cancer cells usually avoid this fate by clustering extra centrosomes in a rough line, allowing a single spindle to form and division to proceed somewhat normally. (redorbit.com)
  • In the current study, the investigators found that when cancer cells with extra centrosomes enter "anaphase" "" the stage of cell division when chromosomes move toward the poles of the spindle before being drawn into the new daughter cells "" a few chromosomes lagged behind the others. (redorbit.com)
  • We showed that even though most cancer cells with extra centrosomes form a single mitotic spindle, they pass through a brief 'multipolar spindle' stage," Ganem said. (redorbit.com)
  • But extra centrosomes could occasionally be seen in the premalignant, metaplastic cells of patients that developed dysplasia or adenocarcinoma. (news-medical.net)
  • Cells with extra centrosomes can then survive and proliferate, giving rise to cells with abnormal numbers of chromosomes that can become malignant cancer cells. (news-medical.net)
  • In 2008, researchers found the first compelling evidence that extra centrosomes could drive tumor formation in flies. (the-scientist.com)
  • However, subsequent studies in mice failed to replicate the results, leading some to question the universality of extra centrosomes' effects. (the-scientist.com)
  • Furthermore, HURP is also required for the clustering of extra centrosomes before division, arguing for a shared molecular requirement of MTOC sorting in mammalian meiosis and cancer cell division. (harvard.edu)
  • A common model proposes that the extra centrosomes that are typically acquired during tetraploidization are responsible for driving tumorigenesis. (elifesciences.org)
  • However, tetraploid cells evolved in culture have been shown to lack extra centrosomes. (elifesciences.org)
  • Here, using a combination of fixed cell analysis, live cell imaging, and mathematical modeling, we show that populations of newly formed tetraploid cells rapidly evolve in vitro to retain a near-tetraploid chromosome number while losing the extra centrosomes gained at the time of tetraploidization. (elifesciences.org)
  • Based on these studies, it has been speculated that the extra centrosomes emerging as a result of tetraploidization may drive chromosomal instability and, in turn, tumorigenesis ( Storchova and Pellman, 2004 ). (elifesciences.org)
  • Following the observation that the number of centrosomes, but not chromosomes, rapidly returns to normal, we combined computational and experimental approaches to identify a specific cellular mechanism that underlies the loss of extra centrosomes. (elifesciences.org)
  • According to Pellman, chromosomal instability, it turns out, "is actually a side effect of the cells' ability to cluster their excess centrosomes. (redorbit.com)
  • Indeed, the genomic instability created by excess centrosomes may help cancer cells to become more malignant. (news-medical.net)
  • Centrosome aberrations as a possible mechanism for chromosomal instability in non-Hodgkin's lymphoma," Leukemia , vol. 17, no. 11, pp. 2207-2213, 2003. (hindawi.com)
  • Centrosome aberrations in chronic myeloid leukemia correlate with stage of disease and chromosomal instability," Leukemia , vol. 19, no. 7, pp. 1192-1197, 2005. (hindawi.com)
  • Here we show that centrosome depletion induces synthetic lethality in cancer cells that contain the 17q23 amplicon, a recurrent copy number aberration that defines about 9% of all primary breast cancer tumours and is associated with high levels of genomic instability 4-6 . (nih.gov)
  • Finally, we find that the overexpression of TRIM37 causes genomic instability by delaying centrosome maturation and separation at mitotic entry, and thereby increases the frequency of mitotic errors. (nih.gov)
  • Collectively, these findings highlight TRIM37-dependent genomic instability as a putative driver event in 17q23-amplified breast cancer and provide a rationale for the use of centrosome-targeting therapeutic agents in treating these cancers. (nih.gov)
  • These results indicate that centrosome defects are a common feature of malignant tumors and suggest that they may contribute to genetic instability in cancer. (aacrjournals.org)
  • Holland said he thinks his team's experiment succeeded because they were able to reach the "sweet spot of instability," given that too many centrosomes can be lethal. (the-scientist.com)
  • Centrosome aberrations after nilotinib and imatinib treatment in vitro are associated with mitotic spindle defects and genetic instability. (druglib.com)
  • We analyzed centrosomes by immunofluorescence and compared to ploidy and chromosomal instability (CIN) as assessed by 6-chromosome FISH in a cohort of 362 breast cancers with median clinical follow-up of 8.4 years. (biomedcentral.com)
  • Using immunocytochemical localization with confocal microscopy, we found ratAurA to be localized at the centrosome in normal and neoplastic tissues of the rat mammary gland. (aacrjournals.org)
  • We identify an N-terminal centrosome localization signal in GEN1, which is required and sufficient for centrosome localization. (ku.dk)
  • These modifications may produce variations in centrosome size (usually too large, due to an excess of pericentriolar material). (wikipedia.org)
  • In 17q23-amplified cells that lack centrosomes, increased levels of TRIM37 block the formation of foci that comprise pericentriolar material-these foci are structures with a microtubule-nucleating capacity that are required for successful cell division in the absence of centrosomes. (nih.gov)
  • Whereas CP110 binding to NEURL4 is dispensable for the regulation of pericentriolar material architecture, its association with HERC2 is required to maintain normal centrosome integrity. (mcponline.org)
  • Centrosome-dependent microtubule nucleation involves the interaction of tubulin subunits with pericentriolar material. (nih.gov)
  • It is likely that the pericentriolar Golgi organization in mammalian cells may serve as a means to connect the Golgi apparatus and the centrosome for the purpose of division. (asm.org)
  • The centrosome orientation checkpoint acts in Drosophila germline stem cells but not their progeny to ensure oriented cell division independent of the spindle assembly checkpoint. (biologists.org)
  • The Centrosome in Drosophila Oocyte Development, T.L. Megraw and T.C. Kaufman . (elsevier.com)
  • The Centrosome in Early Drosophila Embryogenesis, W.F. Rothwell and W. Sullivan . (elsevier.com)
  • Similarly, neuroblast that genetically have been modified such that they lack centrosomes, show a similar defect in polarity orientation memory. (healthcanal.com)
  • The researchers saw similar apical wandering in cells that lack centrosomes due to a mutation in the dsas-4 gene. (rupress.org)
  • The centrosome is a conserved organelle that serves as the microtubule organizing center and regulates many biological processes. (nig.ac.jp)
  • These results suggest that Aurora-A regulates centrosome assembly by controlling the CNN's ability to targeting and/or anchoring gamma-tubulin to the centrosome and organizing microtubule-nucleating sites via its interaction with the COOH-terminal sequence of CNN. (nih.gov)
  • While centrosome fragments are smaller than the fully constituted centrosomes, their microtubule organization function is retained. (ingentaconnect.com)
  • While Golgi and centrosome organization appeared mostly intact in cells lacking GM130, there was a clear separation of these organelles from each other. (bioportfolio.com)
  • Our results reveal the dynamic nature of the centrosome in developing cortical neurons, and implicate centrosome translocation and microtubule organization during the multipolar stage as important determinants of axon formation. (jneurosci.org)
  • Because centrosomes are involved in spindle assembly, they could contribute to chromosome missegregation through the organization of aberrant spindles. (aacrjournals.org)
  • The centrosome plays an important role in microtubule nucleation and organization, ensuring the establishment of cell polarity and balanced chromosome segregation. (aacrjournals.org)
  • In proliferating cells, the centrosome starts duplicating just before, or at, the onset of S phase and the two newly formed centrosomes participate in the assembly and organization of the mitotic spindle, its orientation with respect to cortical cues, and the late events of cytokinesis. (scribd.com)
  • In dividing cells, centrosomes are required for mitotic spindle organization and orientation. (cnrs.fr)
  • In addition to the close dynamic relationship between the ER and Golgi apparatus, a growing interest has been focused on the connection between the Golgi apparatus and the centrosome ( 46 ), a complex and dynamic organelle that functions as the major microtubular organization center ( 18 ). (asm.org)
  • The results established class I HDACs as powerful regulators of microtubule organization, centrosome function, endosome maturation, and infection by IAV and other late penetrating viruses. (prolekare.cz)
  • We propose that a disruption of centrosome integrity and/or spindle organization may play an important role in the development of microcephaly in MCPH2. (biomedcentral.com)
  • She performed pre-and postdoctoral studies with Professor Daniel Mazia at the University of California, Berkeley, who introduced her to the fascinating field of centrosome biology and generated unlimited enthusiasm for centrosome research that she pursued in collaborations with Daniel Mazia and numerous colleagues in cell, molecular, and reproductive biology in the USA, Europe, China, and Latin America. (ebooks.com)
  • The Centrosome: Cell and Molecular Mechanisms of Functions and Dysfunctions in Disease includes chapters on classic and modern aspects of centrosome research to cover topics of current interest that have not been covered in depth in most books on the market so far. (ebooks.com)
  • Our study uncovers the molecular architecture and evolution of the animal centrosome and emphasizes the plasticity of animal cell biology and development. (sciencemag.org)
  • Our goal is to understand the molecular mechanisms of centrosome inheritance and its role in asymmetric cell division. (ki.se)
  • Although the molecular composition of the centrosome has been determined in human and flies, the function of most components is still unclear. (phys.org)
  • Thus, although a comprehensive inventory of centrosome components is missing, emerging evidence indicates that its molecular composition reflects the complexity of its functions. (embopress.org)
  • These studies provide the first atomic insight into a molecular interaction required for mitotic centrosome assembly. (ox.ac.uk)
  • Although centrosome defects have been recognized in tumors for a long time," Pellman said, "it has been a tough problem to rigorously study. (redorbit.com)
  • The Role of the Centrosome in the Development of Malignant Tumors, W.L. Lingle and J.L. Salisbury . (elsevier.com)
  • Over the last few years our understanding of the structure and composition of centrosomes has greatly advanced, and the demonstration of frequent centrosome anomalies in most common human tumors has sparked additional interest in the role of this organelle in a broader scientific community. (worldcat.org)
  • We found that centrosomes in nearly all tumors and tumor-derived cell lines were atypical in shape, size, and composition and were often present in multiple copies. (aacrjournals.org)
  • Recent studies have suggested that the loss of cell polarity and/or chromosome missegregation (aneuploidy) in human malignant tumors could result from defects in centrosome function. (aacrjournals.org)
  • In tumors, 46% of cells showed more than two centrosomes/cell, and ratAurA expression levels coincided with higher centrosome numbers. (aacrjournals.org)
  • Although centrosome aberrations are common in tumors, their consequences remain subject to debate. (embopress.org)
  • Intriguingly, some high-risk tumors have more acentriolar centrosomes, suggesting PCM fragmentation as another mechanism of CA. In vitro induction of CA in two non-transformed human cell lines (MCF10A and RPE) demonstrated that CA induces a de-differentiated cellular state and features of high-grade malignancy, supporting the idea that CA intrinsically causes high-grade tumors. (biomedcentral.com)
  • Here, we demonstrate that integrin signaling is not sufficient to promote rapid microtubule regrowth and that androgen and Src signaling promote γ-tubulin recruitment to the centrosome and microtubule nucleation. (biologists.org)
  • While spindle assembly and centrosome-mediated microtubule nucleation have been extensively studied, much less is known about how centrosome-spindle coupling is achieved. (biologists.org)
  • At the G 2 /M transition, the centrosome must undergo a maturation process where they dramatically increase in size and microtubule nucleation capacity to effectively organize both poles of the mitotic spindle ( 3 ). (mcponline.org)
  • However, exactly how Aurora-A controls the microtubule nucleation onto centrosomes is unknown. (nih.gov)
  • Centrosome alterations in cancer can be divided in two subgroups - i.e., structural or numeric aberrations - yet both can be found simultaneously in a tumor. (wikipedia.org)
  • The researchers found that if they depleted the tumor suppressor p53, cells that chronically lacked Plk4 could divide without centrosomes. (rupress.org)
  • All tumor cell lines had both centrosome defects and abnormal chromsome numbers, whereas neither was observed in nontumor cells. (aacrjournals.org)
  • Taken together, these findings suggest that RINT-1 serves as a novel tumor suppressor essential for maintaining the dynamic integrity of the Golgi apparatus and the centrosome, a prerequisite to their proper coordination during cell division. (asm.org)
  • A strong correlation between CA and high tumor ploidy demonstrates that chromosome and centrosome doubling often occur in concert. (biomedcentral.com)
  • Specifically, inhibition of polo-like kinase 4 (PLK4) using small molecules leads to centrosome depletion, which triggers mitotic catastrophe in cells that exhibit amplicon-directed overexpression of TRIM37. (nih.gov)
  • TAOK inhibition or depletion in centrosome-amplified SKBR3 or BT549 breast cancer cell models increases the mitotic population, the percentages of mitotic cells displaying amplified centrosomes and multipolar spindles, induces cell death, and inhibits cell growth. (aacrjournals.org)
  • HDAC1 depletion reduced the splitting of centrosomes, and enhanced infection. (prolekare.cz)
  • Failure of centrosome regulation can cause mistakes in chromosome segregation and is associated with aneuploidy. (wikipedia.org)
  • Phosphorylation of the yeast centrosome reveals sites of regulation and predicts complex regulation of mammalian centrosomes. (sciencemag.org)
  • She is a cell biologist with research focused on cytoskeletal regulation in various cell systems and on cytoskeletal dysfunctions of the centrosome-microtubule complex that play a role in disease such as cancer and in disorders such as infertility and other reproductive disorders. (ebooks.com)
  • Her studies also included collaborations with NASA scientists and experiments aboard the Space Shuttle Endeavour to examine the effects of spaceflight on centrosome-cytoskeletal regulation during development. (ebooks.com)
  • Along with other areas of focus, he's looking into microtubule regulation and its relationship to another component of the cell called the centrosome. (bio-medicine.org)
  • NEURL4 is a substrate of HERC2, and together these results indicate that the NEURL4-HERC2 complex participates in the ubiquitin-dependent regulation of centrosome architecture. (mcponline.org)
  • Recent work has provided much needed insight into the regulation of centrosome size. (mcponline.org)
  • Our findings provide novel insight into the biological functions of GEN1 by uncovering an important role of GEN1 in the regulation of centrosome integrity. (ku.dk)
  • In cell biology, the centrosome (Latin centrum 'center' + Greek sōma 'body') (also called cytocentre) is an organelle that serves as the main microtubule organizing center (MTOC) of the animal cell, as well as a regulator of cell-cycle progression. (wikipedia.org)
  • Centrosomes are associated with the nuclear membrane during the prophase stage of the cell cycle. (wikipedia.org)
  • The centrosome replicates during the S phase of the cell cycle. (wikipedia.org)
  • Some cell types arrest in the following cell cycle when centrosomes are absent. (wikipedia.org)
  • As the cell cycle progresses, the centrosome undergoes a series of morphological and functional changes. (wikipedia.org)
  • The centrosome cycle consists of four phases that are synchronized to the cell cycle. (wikipedia.org)
  • This link between the cell cycle and the centrosome cycle is mediated by cyclin-dependent kinase 2 (Cdk2). (wikipedia.org)
  • Throughout the cell cycle, centrosomes in germline stem cells (GSCs) are oriented within their niche and this ensures asymmetric division. (nature.com)
  • We found that GSCs containing misoriented centrosomes accumulate with age and that these GSCs are arrested or delayed in the cell cycle. (nature.com)
  • The cell cycle arrest is transient, and GSCs appear to re-enter the cell cycle on correction of centrosome orientation. (nature.com)
  • On the basis of these findings, we propose that cell cycle arrest associated with centrosome misorientation functions as a mechanism to ensure asymmetric stem cell division, and that the inability of stem cells to maintain correct orientation during ageing contributes to the decline in spermatogenesis. (nature.com)
  • The centrosome is copied only once per cell cycle . (wikipedia.org)
  • Some cell types arrest in the following cell cycle when centrosomes are absent, though this doesn't always happen. (wikipedia.org)
  • The Coordination of Centrosome Reproduction with Nuclear Events during the Cell Cycle, G. Sluder and E.H. Hinchcliffe . (elsevier.com)
  • However, the relationship between cell-cycle regulators and centrosome duplicating factors is not well understood. (sigmaaldrich.com)
  • In each cell cycle, a cell duplicates its centrosome, producing a pair of the structures that can serve as the poles of the mitotic spindle. (rupress.org)
  • In each cell cycle the centrosome duplicates once and only once in a semi-conservative fashion much like the DNA in the nucleus. (biologists.com)
  • Remarkably, centrosomins regulate not only centrosome assembly and their functions in cytoskeleton assembly, but also the replication of centrosomes in the cell cycle. (bio-medicine.org)
  • Centrosome biogenesis and function is tightly regulated during the cell cycle. (mcponline.org)
  • Centrosomes are microtubule-organizing centers that function at multiple stages of the cell cycle. (cnrs.fr)
  • nevertheless it contains two centrosomes of different ages, as every centrosome is duplicated once during the cell cycle, resulting in the presence of an old and young centrosome at mitotic onset ( Nigg and Stearns, 2011 ). (elifesciences.org)
  • Balczon R, Bao L, Zimmer WE (1994) PCM-1, a 228-kD centrosome autoantigen with a distinct cell cycle distribution. (springer.com)
  • The centrosome plays a key role in chromosome segregation and cell cycle checkpoint control ( 30 ), while the fragmentation of the Golgi apparatus is required for the mitotic phase entry ( 9 , 50 ). (asm.org)
  • Centrosomes are very dynamic organelles duplicating, maturing, and separating in stages coupled with cell cycle progression. (asm.org)
  • Winey, M 1999, ' Cell cycle: Driving the centrosome cycle ', Current Biology , vol. 9, no. 12. (elsevier.com)
  • We also observed that the absence of the centrosome leads to defects in cytokinesis. (sciencemag.org)
  • Centrosome defects have been associated with many diseases, such as ciliopathies, polycystic kidney disease and cancer. (cnrs.fr)
  • Structural and functional defects of centrosomes are associated with cancer ( 1, 2 ). (aacrjournals.org)
  • Indeed, CA and other centrosome defects have been reported in diverse cancer types [ 3 , 5 ]. (biomedcentral.com)
  • Theodor Boveri, in 1914, described centrosome aberrations in cancer cells. (wikipedia.org)
  • Usually, structural aberrations appear due to uncontrolled expression of centrosome components, or due to post-translational modifications (such as phosphorylations) that are not adequate for the components. (wikipedia.org)
  • All of this emerging evidence suggests that targeting centrosome aberrations may be a future avenue for therapeutic intervention in cancer research. (dovepress.com)
  • We demonstrate that NLP ‐induced structural centrosome aberrations trigger the escape ("budding") of living cells from epithelia. (embopress.org)
  • Second, atomic force microscopy reveals that cells harboring these centrosome aberrations display increased stiffness. (embopress.org)
  • As a consequence, mitotic cells are pushed out of mosaic epithelia, particularly if they lack centrosome aberrations. (embopress.org)
  • We conclude that centrosome aberrations can trigger cell dissemination through a novel, non‐cell‐autonomous mechanism, raising the prospect that centrosome aberrations contribute to the dissemination of metastatic cells harboring normal centrosomes. (embopress.org)
  • NLP ‐induced structural centrosome aberrations trigger budding of mitotic cells from polarized epithelia. (embopress.org)
  • Budding mitotic cells need not themselves harbor centrosome aberrations. (embopress.org)
  • Recently, we have demonstrated that the tyrosine kinase inhibitor imatinib induces centrosome and chromosome aberrations in vitro. (druglib.com)
  • Therapeutic doses of imatinib and/or nilotinib administered separately, consecutively or in combination similarly induced centrosome, mitotic spindle, and karyotype aberrations. (druglib.com)
  • These findings highlight the importance of centrosome aberrations in the biology of human breast cancer. (biomedcentral.com)
  • Centrosome aberrations cause human diseases including ciliopathies that arise from mutations in genes encoding centrosome components, such as primary ciliary dyskinesia, autosomal recessive primary microcephaly, polycystic kidney disease, and Bardet-Biedl disease [ 2 ]. (biomedcentral.com)
  • Cells begin to accumulate centrosomes-;organelles that play a vital role during cell division-;before they transform into cancer cells, according to a new study of patients with Barrett's esophagus condition, which is associated with esophageal cancer. (news-medical.net)
  • However, most of these conditions have not only separated these two organelles, but also caused extensive fragmentation of the Golgi, making it difficult to dissect the specific contribution of Golgi-centrosome proximity. (bioportfolio.com)
  • Centrosomes are tiny cellular organelles that nucleate microtubule growth and organize the mitotic spindle for segregating chromosomes into daughter cells. (aacrjournals.org)
  • A hallmark of cell polarity is the reorientation of the centrosome that allows repositioning of organelles and vesicles in an asymmetric fashion. (pasteur.fr)
  • While centrosomes can separate in prophase or in prometaphase after nuclear envelope breakdown (NEBD), prophase centrosome separation optimizes spindle assembly and minimizes the occurrence of abnormal chromosome attachments that could end in aneuploidy [7, 8]. (deepdyve.com)
  • The centrosome is thought to have evolved only in the metazoan lineage of eukaryotic cells. (wikipedia.org)
  • Centrosomes are the major microtubule organizing centers (MTOC) in mammalian cells. (wikipedia.org)
  • The centrosome cycle is important to ensure that daughter cells receive a centrosome after cell division. (wikipedia.org)
  • In normal cells, which have two centrosomes, division occurs as the pairs of chromosomes split neatly apart, like halves of a zipper, each set moving into one of the daughter cells. (redorbit.com)
  • In normal cells, the two centrosomes serve as the polar ends of the spindle, the chromosomes arrayed between them like ranks of twin soldiers. (redorbit.com)
  • Cells with more than two centrosomes enter a "multipolar" phase with several axes along which division may take place. (redorbit.com)
  • The centrosome has apparently only evolved in animal cells. (wikipedia.org)
  • Centrosome Replication in Somatic Cells: The Significance of the G1 Phase, R. Balczon . (elsevier.com)
  • Centrosomes play an integral role in the growth of cells and the ultimate development of many animals, and sometimes plants. (elsevier.com)
  • In addition to the normal growth of cells, centrosomes can also play a key role in the spread of cancer and are of increased interest to both the genetics and oncology communities. (elsevier.com)
  • Cells with too many centrosomes usually fail to divide properly and die. (news-medical.net)
  • Cancer cells often contain excessive numbers of centrosomes, however, and usually survive cell division despite their propensity to form abnormal spindles and missegregate chromosomes. (news-medical.net)
  • The most mutated gene in human cancers, p53 is thought to kill cells with too many centrosomes. (news-medical.net)
  • Double-label immunofluorescent microscopy of centrosomes in Caski cells. (pnas.org)
  • Function of Golgi-centrosome proximity in RPE-1 cells. (bioportfolio.com)
  • The close physical proximity between the Golgi and the centrosome is a unique feature of mammalian cells that has baffled scientists for years. (bioportfolio.com)
  • These results suggest that Golgi-centrosome proximity per se is not necessary for the normal function of RPE-1 cells. (bioportfolio.com)
  • We investigated whether similar spatial controls involving the centrosome (the functional equivalent of the SPB) might operate in vertebrate cells, which are much larger than yeast cells. (sciencemag.org)
  • This theme issue focuses on the study of centrosomes in animal cells, covering progress from different species and cell types. (royalsocietypublishing.org)
  • Furthermore, the crucial roles played by the centrosome in stem cells and during development, as well as in disease, are examined. (royalsocietypublishing.org)
  • Importantly, an increase in passage of the 14-3-3γ-knockdown cells led to an increase in the number of cells containing clustered centrosomes leading to the generation of pseudo-bipolar spindles. (sigmaaldrich.com)
  • The second is the paper's scientific theme: the origin of the centrosome, a component of animal cells that functions in cell division. (innovations-report.com)
  • The process is slower in cells missing a centrosome (right). (rupress.org)
  • hypothesized that cells have a centrosome surveillance system to protect against harmful mitoses that arise from divisions with the wrong number of centrosomes. (rupress.org)
  • Transfection of p53 into PC3 cells resulted in a decreased cell growth rate, G2/M arrest and decreased centrosome abnormalities. (nih.gov)
  • 000182433 001__ 182433 000182433 005__ 20190316235529.0 000182433 0247_ $$2doi$$a10.1242/jcs.01128 000182433 022__ $$a0021-9533 000182433 037__ $$aARTICLE 000182433 245__ $$aThe arithmetic of centrosome biogenesis 000182433 269__ $$a2004 000182433 260__ $$bCompany of Biologists$$c2004 000182433 336__ $$aReviews 000182433 520__ $$aHow do cells regulate centrosome number? (epfl.ch)
  • Therefore, we examined centrosomes in human pancreatic tissue sections obtained from patients with ductal carcinoma and other pathological states to evaluate whether centrosome abnormalities are specific for cancer cells in situ , and thus the presence of such abnormalities could be a sensitive diagnostic marker. (aacrjournals.org)
  • The results demonstrated that almost all pancreatic ductal carcinomas and some adenomas exhibited a striking defect in centrosome profiles, whereas normal pancreatic tissues and ductal cells of chronic pancreatitis tissues did not. (aacrjournals.org)
  • Interestingly, the mother and daughter centrosomes are non-randomly inherited in some stem cells, and this process is essential to endow stemness to one of the sibling cells. (ki.se)
  • How do cells distinguish between mother and daughter centrosomes? (ki.se)
  • The centrosome, a small organelle, is a key microtubule organising centre in cells. (biologists.com)
  • Centrosomes play important roles both in cycling and non-cycling cells: in the former they participate in building the bipolar mitotic spindle, whereas in the latter they modulate the assembly of the primary cilium, a structure implicated in sensing and signalling. (biologists.com)
  • Does the centrosome have different roles in symmetrically and asymmetrically dividing cells? (biologists.com)
  • this ensures the faithful segregation of the genome and centrosomes to the daughter cells. (biologists.org)
  • The freshwater flatworm Schmidtea mediterranea lives in southern Europe and Northern Africa is the first animal ever discovered without a crucial structure inside its cells known as the centrosome. (phys.org)
  • Normal ductal epithelium and stromal cells displayed an expected complement of one to two centrosomes/cell, whereas comparable cells in methylnitrosourea-treated animals displayed significantly elevated centrosome numbers. (aacrjournals.org)
  • Centrosomes are the main microtubule‐organizing centers of animal cells. (embopress.org)
  • 1 Centrosomes are the major microtubule organizing centers in mammalian cells and participate in various cellular processes that include cell motility, mitotic cell division, and ciliogenesis. (mcponline.org)
  • studied symmetrical division of human cells using fluorescent tags that made it possible to tell the centrosomes apart. (elifesciences.org)
  • Moreover, in case the two chromosome copies fail to separate properly as cells divide, the older centrosome is more likely to receive both chromosome copies at the expense of the other centrosome. (elifesciences.org)
  • s findings show that the age of the centrosomes leads to asymmetry in all cell divisions, even those that produce cells that are destined to have the same role in an organism. (elifesciences.org)
  • The fact that one centrosome is permanently positioned in the neuroblast opposing the side of the meuroblast where daughter cells bud off, led González's group to focus on this organelle and its possible role in the transmission of polarity during the division of these stem cells. (healthcanal.com)
  • Consequently, drugs that stimulate centrosome declustering and induce multipolarity are likely to target dividing centrosome-amplified cancer cells preferentially, while sparing normal bipolar cells. (aacrjournals.org)
  • This observation raises questions about how tetraploid cells evolve and more specifically about the mechanisms(s) underlying centrosome loss. (elifesciences.org)
  • This appears to happen through a process of natural selection in which tetraploid cells that inherit a single centrosome during a bipolar division with asymmetric centrosome clustering are favored for long-term survival. (elifesciences.org)
  • have indicated that clones of tetraploid or near-tetraploid cells displayed normal centrosome numbers. (elifesciences.org)
  • This suggests that our understanding of the evolution of tetraploid cells is incomplete and how centrosome and chromosome numbers evolve after tetraploidization needs to be revisited. (elifesciences.org)
  • To address this problem, we studied the time period immediately following cytokinesis failure and investigated how centrosome and chromosome numbers change in newly formed tetraploid cells. (elifesciences.org)
  • ILK fails to localize to the centrosomes of abnormal spindles in RUVBL1-depleted cells. (lancs.ac.uk)
  • Centrosomes perform a variety of different cellular functions: they are the main microtubule organising centre in animal cells and are important signalling hubs. (ox.ac.uk)
  • Induction of Excess Centrosomes in Neural Progenitor Cells during the Development of Radiation-Induced Microcephaly. (nii.ac.jp)
  • Roig, Joan 2018-01-08 00:00:00 Centrosomes [1, 2] play a central role during spindle assembly in most animal cells [3]. (deepdyve.com)
  • In 4.1R-depleted mitotic cells, efficient centrosome separation is reduced, resulting in monopolar spindle formation. (asm.org)
  • Following serum starvation for 1 h, cells were fixed with PFA and stained with antibody against p150 Glued to mark the centrosome (red). (biomedcentral.com)
  • We established a method to identify centrosomes at the single-cell level in clinical samples and found that centrosome number abnormalities arise early in Barrett's esophagus progression,' Mesquita says. (news-medical.net)
  • Centrosome abnormalities are emerging hallmarks of cancer. (bioportfolio.com)
  • These findings suggest that centrosome abnormalities may develop at a relatively early stage of pancreatic ductal carcinogenesis. (aacrjournals.org)
  • These results suggest that centrosome abnormalities can occur early in the multistep process of pancreatic ductal carcinogenesis and that detection of these abnormalities may be of value for assessing the underlying malignant potential in pancreatic lesions. (aacrjournals.org)
  • We found that most (85%) carcinomas and some adenomas displayed abnormal centrosome profiles, characterized by an increase in size and number of centrosomes, and by their irregular distribution. (aacrjournals.org)
  • In 1991, we postulated a hypothesis that if a defective male centrosome is inherited by a human oocyte, it might lead to abnormal cleavage and compromise embryonic development (11). (thefreedictionary.com)
  • Aberrant numbers of centrosomes in a cell have been associated with cancer. (wikipedia.org)
  • The centrosome cycle has been found to be regulated by multiple things, including reversible phosphorylation and proteolysis. (wikipedia.org)
  • Nucleophosmin is only found in unreplicated centrosomes and its phosphorylation by Cdk2/cyclin E removes NPM from the centrosomes, initiating procentriole formation. (wikipedia.org)
  • Long-term disruption of CP110 phosphorylation leads to unscheduled centrosome separation and overt polyploidy. (thebiogrid.org)
  • Nek9 Phosphorylation Defines a New Role for TPX2 in Eg5-Dependent Centrosome Separation before. (deepdyve.com)
  • This delays the alignment of the chromosomes that are connected to the old centrosome, as this process requires a flexible attachment. (elifesciences.org)
  • Recent studies have shown that centrosomes have an unexpected new role in asymmetric cell division. (ki.se)
  • In asymmetric stem cell divisions, the age of centrosomes affects their behaviour and their probability to remain in the stem cell. (elifesciences.org)
  • In the current work, we use in situ live imaging to demonstrate that the centrosome and the accompanying polarized cytoplasm exhibit apical translocation in newborn cortical neurons preceding initial axon outgrowth. (jneurosci.org)
  • Here we found that in resting lymphocytes, centrosome-associated Arp2/3 locally nucleates F-actin, which is needed for centrosome tethering to the nucleus via the LINC complex. (pasteur.fr)
  • It's not yet clear whether the role of the centrosome in polarity determination is microtubule-dependent or independent. (wikipedia.org)
  • It is therefore of interest to understand whether axon formation follows this principle of polarity, and whether the centrosome relocates toward the site of axon formation in the developing cortex. (jneurosci.org)
  • They also form the core of the centrosome, which organizes microtubule arrays important for cell shape, polarity, motility and division. (uniprot.org)
  • These experiments indicate that the centrosome functions in the mechanisms that serves as a polarity orientation memory over many cell divisions. (healthcanal.com)
  • This Review discusses the multiple roles played by centrosomes during embryonic growth of the vertebrate central nervous system, highlighting the links between centrosome dysfunction and microcephaly. (biologists.org)
  • The Centrosome of the Early C. elegans Embryo: Inheritance, Assembly, Replication, and Developmental Roles, K.F. O'Connell . (elsevier.com)
  • Centrosomes play crucial roles in a wide range of cellular processes by organizing the cell's microtubule cytoskeleton. (news-medical.net)
  • The centrosome plays key roles in neuronal progenitor proliferation and fate determination, as well as neuronal differentiation and migration ( Higginbotham and Gleeson, 2007 ). (biologists.org)
  • Centrosomes play fundamental roles in mitotic spindle organisation, chromosome segregation and maintenance of genetic stability. (druglib.com)
  • USP44 inhibited chromosome segregation errors independent of its role in the mitotic checkpoint by regulating centrosome separation, positioning, and mitotic spindle geometry. (jci.org)
  • Upon division, each daughter cell receives one centrosome. (wikipedia.org)
  • This will be relevant for a better understanding of how centrosomes function in the progression of cancer and other diseases. (epfl.ch)
  • The researchers never saw excess centrosomes in normal esophageal tissue. (news-medical.net)
  • alpha- and beta-tubulin, ch-TOG (XMAP215), and RUVBL1 associate with ILK and colocalize with it to mitotic centrosomes. (lancs.ac.uk)
  • Centrosomes were isolated from Spisula oocyte lysates by a discontinuous two-step sucrose gradient centrifugation system, consisting of 66 and 52.5% sucrose steps, similar to that used for isolation of mammalian centrosomes (Mitchison and Kirschner, 1984). (nih.gov)
  • TgCep250 is dynamically processed through the division cycle and essential for structural integrity of the Toxoplasma centrosome. (bioportfolio.com)
  • Structural Basis for Mitotic Centrosome Assembly in Flies. (ox.ac.uk)
  • The poles of the mitotic spindle contain one old and one young centrosome. (elifesciences.org)
  • The centrosome is a small cytoplasmic organelle discovered by Edouard van Beneden, and further named and described by Boveri in the late 19th century. (dovepress.com)
  • As an organelle coupling nuclear and cytoplasmic divisions, the centrosome is essential to mitotic fidelity, and its inheritance could be critical to understanding cell transformation. (sciencemag.org)
  • Together with recent results in yeasts, our data point to a conserved centrosome-dependent pathway that integrates spatial controls into the decision of completing cell division, which requires the repositioning of the centrosome organelle. (sciencemag.org)
  • We suggested that it might play an important role in the formation of the primary cilium, the organelle obligatorily associated with the centrosome. (springer.com)
  • These studies provide a direct link between centrosomes and tumorigenesis. (aacrjournals.org)
  • It's nice now that both fly and mouse show that if you amplify centrosomes you can promote tumorigenesis," says the University of Oxford's Jordan Raff , a coauthor of the 2008 study, "but it's still not very clear how important that is for human cancers. (the-scientist.com)
  • There are also alternative pathways of centrosome biogenesis. (epfl.ch)
  • We mainly focus on understanding the mechanisms of centrosome biogenesis and dynamics by using the combination of innovative and multi-disciplinary approaches. (nig.ac.jp)
  • However, researchers haven't been able to confirm that centrosomes help organize the mitotic spindle. (rupress.org)
  • The presence of functional centrosomes is therefore important for cell physiology. (biologists.com)
  • The disassembly and reassembly of functional centrosomes in vitro. (semanticscholar.org)