Centrosome: 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).Centrioles: 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.Spindle Apparatus: 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.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.Mitosis: 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.Tubulin: 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.Microtubule-Organizing Center: 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.Microtubule-Associated Proteins: 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.Aurora Kinases: 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.Interphase: 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).Aurora Kinase A: 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.Cell Cycle Proteins: 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.Cell Cycle: 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.Chromosomal Instability: An increased tendency to acquire CHROMOSOME ABERRATIONS when various processes involved in chromosome replication, repair, or segregation are dysfunctional.Dyneins: 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.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Nocodazole: Nocodazole is an antineoplastic agent which exerts its effect by depolymerizing microtubules.Aneuploidy: 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).HeLa Cells: 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, Fluorescence: 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.Prophase: 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.Chromosome Segregation: The orderly segregation of CHROMOSOMES during MEIOSIS or MITOSIS.Kinesin: 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.-.Cytokinesis: The process by which the CYTOPLASM of a cell is divided.Cell Polarity: 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.Cell Nucleus: 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)Metaphase: The phase of cell nucleus division following PROMETAPHASE, in which the CHROMOSOMES line up across the equatorial plane of the SPINDLE APPARATUS prior to separation.Microtubule Proteins: Proteins found in the microtubules.Embryo, Nonmammalian: The developmental entity of a fertilized egg (ZYGOTE) in animal species other than MAMMALS. For chickens, use CHICK EMBRYO.Cilia: Populations of thin, motile processes found covering the surface of ciliates (CILIOPHORA) or the free surface of the cells making up ciliated EPITHELIUM. Each cilium arises from a basic granule in the superficial layer of CYTOPLASM. The movement of cilia propels ciliates through the liquid in which they live. The movement of cilia on a ciliated epithelium serves to propel a surface layer of mucus or fluid. (King & Stansfield, A Dictionary of Genetics, 4th ed)Fluorescent Antibody Technique: 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.Kinetochores: Large multiprotein complexes that bind the centromeres of the chromosomes to the microtubules of the mitotic spindle during metaphase in the cell cycle.Parthenogenesis: 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.Anaphase: The phase of cell nucleus division following METAPHASE, in which the CHROMATIDS separate and migrate to opposite poles of the spindle.RNA Interference: 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.Nuclear Proteins: 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.Genomic Instability: An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional.Cell Nucleus Division: The process by which the CELL NUCLEUS is divided.Nuclear Envelope: 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).Cyclin E: A 50-kDa protein that complexes with CYCLIN-DEPENDENT KINASE 2 in the late G1 phase of the cell cycle.Drosophila Proteins: 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.Protein Transport: 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.Cyclin-Dependent Kinase 2: 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.RNA, Small Interfering: 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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Fertilization: The fusion of a spermatozoon (SPERMATOZOA) with an OVUM thus resulting in the formation of a ZYGOTE.Green Fluorescent Proteins: 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.Xenopus Proteins: 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.Polyploidy: The chromosomal constitution of a cell containing multiples of the normal number of CHROMOSOMES; includes triploidy (symbol: 3N), tetraploidy (symbol: 4N), etc.Caenorhabditis elegans: A species of nematode that is widely used in biological, biochemical, and genetic studies.Chromosomes: 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)CDC2 Protein Kinase: 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.Caenorhabditis elegans Proteins: 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.Drosophila: 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.Telophase: 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.Cyclin A: 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.Cytoskeletal Proteins: 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.Drosophila melanogaster: A species of fruit fly much used in genetics because of the large size of its chromosomes.Cytoplasm: 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 Fusion Proteins: 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.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Meiosis: 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.Organoids: An organization of cells into an organ-like structure. Organoids can be generated in culture. They are also found in certain neoplasms.Zygote: The fertilized OVUM resulting from the fusion of a male and a female gamete.Protein Binding: 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.Molecular Sequence Data: 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.Starfish: Echinoderms having bodies of usually five radially disposed arms coalescing at the center.Models, Biological: 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.Oocytes: 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)

*Centrosome

The centrosome is thought to have evolved only in the metazoan lineage of eukaryotic cells. Fungi and plants lack centrosomes ... 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 structures ... Unlike centrioles, centrosomes are required for survival of the organism. Cells without centrosomes lack radial arrays of ...

*Centrosome cycle

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, so that by the time mitosis occurs there are two centrosomes ... The centrosome cycle is important to ensure that daughter cells receive a centrosome after cell division. As the cell cycle ... Centrosomes are the major microtubule organizing center (MTOC) in mammalian cells. Failure of centrosome regulation can cause ...

*KIF15

Centrosome, 3D. "Centrosome 3D Consortium". Research Lab. "Research of Thomas Mayer". University of Konstanz. ... thought to promote spindle assembly by cross-linking and sliding along microtubules creating a separation between centrosomes. ...

*Centriole

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 ... Centrioles are a very important part of centrosomes, which are involved in organizing microtubules in the cytoplasm. The ... Delattre, M; Gönczy, P (2004). "The arithmetic of centrosome biogenesis". Journal of Cell Science. 117 (Pt 9): 1619-30. doi: ...

*Ninein-like protein

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. ...

*ADP-ribosylation

PARP3 is involved in centrosome regulation. Tankyrase is another ADP-ribose polymerase that is involved in telomere length ...

*Mónica Bettencourt-Dias

2011). "Centrosomes and cilia in human disease". Trends in Genetics. 27 (8): 307-315. doi:10.1016/j.tig.2011.05.004. ... 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): 1-7. doi:10.1186/1741-7007-11-28 ...

*Feline foamy virus

Afonso, PV; Zamborlini, A; Saïb, A; Mahieux, R (14 April 2007). "Centrosome and retroviruses: the dangerous liaisons". ...

*CEP68

... 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/ ...

*Spindle apparatus

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 ...

*Cytoskeleton

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 ...

*Actomyosin ring

Pelletier, L., & Yamashita, Y. (2012). Centrosome asymmetry and inheritance during animal development. Current Opinion In Cell ...

*PCM1

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), ...

*Oogenesis

Manandhar G, Schatten H, Sutovsky P (January 2005). "Centrosome reduction during gametogenesis and its significance". Biol. ... Vejledning om kunstig befrugtning 2006 (Danish) Bibliography Manandhar G, Schatten H and Sutovsky P (2005). Centrosome ... occurs completely without the aid of spindle-coordinating centrosomes. The creation of oogonia traditionally doesn't belong to ...

*STK38

Hergovich A, Lamla S, Nigg EA, Hemmings BA (2007). "Centrosome-associated NDR kinase regulates centrosome duplication". Mol. ...

*BRSK1

"SADB phosphorylation of gamma-tubulin regulates centrosome duplication". Nature Cell Biology. 11 (9): 1081-92. doi:10.1038/ ...

*USP9X

"USP9X regulates centrosome duplication and promotes breast carcinogenesis". Nature Communications. 8. doi:10.1038/ncomms14866. ...

*Spindle checkpoint

... when one kinetochore becomes attached to one centrosome, the sister kinetochore becomes exposed to the centrosome located in ... Mayor, T; Meraldi, P; Stierhof, YD; Nigg, EA; Fry, AM (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 ... During S phase, the centrosome starts to duplicate. Just at the beginning of mitosis, both centrioles achieve their maximal ...

*Multipolar spindles

Sato, Norihiro (2004). "Radiation Therapy and Centrosome Anomalies in Pancreatic Cancer". In Erich A. Nigg. Centrosomes in ... 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 ...

*RANBP1

2004). "Mammalian RanBP1 regulates centrosome cohesion during mitosis". J. Cell Sci. 116 (Pt 16): 3399-411. doi:10.1242/jcs. ...

*TUBG1

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 ... "A direct interaction with NEDD1 regulates gamma-tubulin recruitment to the centrosome". PLoS One. 5 (3): e9618. doi:10.1371/ ... "Sequential phosphorylation of Nedd1 by Cdk1 and Plk1 is required for targeting of the gammaTuRC to the centrosome". Journal of ...

*CEP192

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. ...

*Phaeoceros laevis

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 ...

*Spindle pole body

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. ...

*Rootletin

It also helps to contribute to the centrosome cohesion before mitosis. Expression of rooletin leads to the formation of fibrous ... Rootletin is a component of the ciliary rootlet, and, together with CEP68 and CEP250, is required for centrosome cohesion. ... Lim HH, Zhang T, Surana U (July 2009). "Regulation of centrosome separation in yeast and vertebrates: common threads". Trends ... 2003). "Proteomic characterization of the human centrosome by protein correlation profiling". Nature. 426 (6966): 570-4. doi: ...
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
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 ...
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.
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
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 ...
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 ...
Centrosome amplification (CA) is a hallmark of virtually all types of cancers including solid tumors and hematological malignancies. Cancer cells with extra centrosomes use centrosome clustering (CC) to allow for successful division. Because normal cells do not rely on this mechanism, CC is regarded as a promising target to selectively eradicate cells harboring supernumerary centrosomes. To identify novel inhibitors of CC, we developed a cell-based high-throughput screen that reports differential drug cytotoxicity for isogenic cell populations with different centrosome contents. We identified CP-673451 and crenolanib, two chemically related compounds originally developed for inhibition of PDGFR-β, as robust inhibitors of CC with selective cytotoxicity for cells with extra centrosomes. We demonstrate that these compounds induce mitotic spindle multipolarity by activation of the actin severing protein cofilin, leading to destabilization of the cortical actin network, and provide evidence 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 ...
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.. ...
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 ...
Here, we show that Cdk5rap2 is mutated in the Hertwigs anemia mouse, and we demonstrate that Cdk5rap2 is essential for normal progenitor proliferation and survival in the cerebral cortex. Cdk5rap2an/an animals have smaller cerebral cortices that result from an overall reduction of the neuronal layers caused by a decrease in progenitor numbers. Increases in both cell death and premature cell cycle exit reduce the cortical precursor population. Moreover, the decrease of neuronal progenitors in Cdk5rap2an/an animals correlates, paradoxically, with an increased mitotic index, suggesting delays in mitotic progression. We found altered mitotic orientation as well as increased abnormal mitotic figures, with aneupolar spindles, implicating essential roles for Cdk5rap2 in spindle and centrosome function during neurogenesis. These data suggest that CDK5RAP2 mutations in humans could cause microcephaly by mechanisms that include not only mitotic arrest and cell death, but also may include defects in cell ...
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 ...
The antitumor drug etoposide (ETO) is widely used in treating several cancers including adrenocortical tumor (ACT). the autophagy inhibitor reduced Take action cell growth and inhibited ETO-induced centrosome amplification. Chloroquine alleviated CDK2 and ERK but not Chk2 activation and thus inhibited centrosome amplification in either ETO- or hydroxyurea-treated ACT cells. In addition chloroquine also inhibited centrosome amplification in osteosarcoma U2OS cell lines when treated with ETO or hydroxyurea. In summary we have exhibited that chloroquine inhibited ACT cell growth and alleviated DNA damage-induced centrosome amplification by inhibiting CDK2 and ERK activity thus preventing genomic instability and recurrence of ACT. Introduction Adrenal gland which is composed of the cortex and medulla is the most important endocrine organ that lies on top of the kidney. Adrenocortex is the major site of steroidogenesis in response to adrenocorticotropic hormone stimulation and its abnormal growth ...
Overexpression of Klf4 suppresses centrosome amplification in Klf4−/−MEFs. Centrosome staining was conducted with an antibody against γ-tubulin and detecte
Forces involved in the positioning of the centrosome. Pulling forces applied to the MTs at the cell cortex by dynein act to position the centrosome at the cell
Accessory nuclei bud off from the membrane of the nucleus, the cellular structure that contains the chromosomes. By the time the egg is fully developed, it contains several hundred accessory nuclei that look much like the nucleus except that they dont contain chromosomes. Late in the development of the egg cell, the accessory nuclei disintegrate and centrosomes appear in the same locations in the cell. "Right before the egg is laid, the membranes of the accessory nuclei break down, and at the same time the centrosomes begin to form," Ferree said. One of the most striking aspects of this mechanism is the large number of accessory nuclei and centrosomes that form in the developing eggs of these Hymenopteran insects. "You only need two centrosomes, and they make hundreds of them. So they go through a lot of work to make a male," Sullivan said. "A lot of energy goes into making these centrosomes, and if the egg gets fertilized they dont use them--the centrosome from the sperm is used ...
... is a novel centrosomal protein present in the connecting piece region of human sperm that is transmitted to the zygote and can be detected throughout the first mitotic division ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
CETN1 Full-Length MS Protein Standard (NP_004057), Labeled with [U- 13C6, 15N4]-L-Arginine and [U- 13C6, 15N2]-L-Lysine, was produced in human 293 cells (HEK293) with fully chemically defined cell culture medium to obtain incorporation efficiency at Creative-Proteomics. The protein encoded by this gene plays important roles in the determination of centrosome position and segregation, and in the process of microtubule severing. This encoded protein is localized to the centrosome of interphase cells, and redistributes to the region of the spindle poles during mitosis, reflecting the dynamic behavior of the centrosome during the cell cycle.
The protein encoded by this gene can interact with gamma-tubulin and PP1 phosphatase, a regulator of centrosome separation. The encoded protein is a positive regulator of PP1 phosphatase and thus plays a role in the control of centrosome integrity. [provided by RefSeq, Feb 2017] ...
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.
Cyclin E activates Cdk2, controls centrosome duplication and regulates histone gene transcription. Cyclin E is deregulated in cancer and appears as low molecular weight (LMW) isoforms that correlate strongly with decreased survival in breast cancer patients. Transgenic mice overexpressing LMW cyclin E have increased incidence of mammary tumors and distant metastasis when compared to full length cyclin E. To specifically test the requirement for Cdk2 in LMW-cyclin E mediated mammary tumorigenesis, we generated transgenic mice, which expressed LMW-cyclin E in a Cdk2 deficient background. We found that mammary gland development proceeds relatively normally in these animals, indicating that Cdk2 kinase activity is largely dispensable for this process. However, Cdk2 deficient mice were completely resistant to LMW-cyclin E mediated mammary tumors. Cdk2 wild-type or heterozygous mice succumbed to mammary tumors with mean latencies of 16 and 19.5 months, respectively, but Cdk2 nullizygous littermates ...
...TALLAHASSEE Fla. -- If you dont know how a human cell is supposed to...Tim Megraw a veteran researcher who joined the College of Medicine as...The focus of Megraws work is cell division. Cancer occurs when renega... Were studying how microtubules are regulated in cells normally Meg...,Researcher,awarded,$1.2,million,grant,to,study,centrosomes,and,cilia,biological,biology news articles,biology news today,latest biology news,current biology news,biology newsletters
Anti-Pericentrin antibody [mAbcam 28144] - Centrosome Marker (ab28144) has been cited in 35 publications. References for Human, ChHm in ICC/IF, IF, WB
Find all books from Heide Schatten - The Centrosome. At find-more-books.com you can find used, antique and new books, COMPARE results and immediately PURCHASE your selection at the best price. 9781627030359
The laboratory of Dr. Eva Kiermaier is seeking for highly motivated PhD students (m/f, paycale TVL 13 65%) who aim to conduct their PhD thesis in a multidisciplinary field. The lab focuses on different aspects of centrosome biology in immune cells and its relationship to cancer development. Centrosomes are small organelles, which nucleate and organize the microtubule...
Contributes to mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis as part of the HAUS augmin-like complex.
The growing number of reported substrates indicates complexity of Plk1 regulation and the significant role of Plk1 in different stages of mitosis and beyond. Plk1 is found in several locations throughout most of the cell cycle and its main functions start in G2, during which it localizes to centrosomes. Further, Plk1 is important for regulating mitotic entry in vertebrates. In prophase, Plk1 acts on multiple points. It activates cdk1 by removing its inhibitory phosphorylation by activating the Cdc25c phosphatase (Toyoshima-Morimoto,2002). Moreover, it inactivates Wee1 (Watanabe,2004) and Myt1 (Inoue,2005) through their phosphorylation. Plk1 is also involved in regulating the spindle morphology through γ-tubulin recruitment to centrosomes. Plk1 helps in tubulin nucleation by interacting with many proteins and phosphorylating them. Plk1 recruits PCM proteins like CEP192, pericentrin, CEP215 and Nedd1 that are involved in γ‑tubulin recruitment and PCM reorganization (Zhang,2009). Plk1 ...
Using a fungus two-hybrid system, we isolated a book human centrosomal protein, CPAP (centrosomal P4. utilized to display screen for protein that connect to 4.1R-135. The top domains (HD; residues 1 to 209) of 4.1R-135 (4.1R-HD) was fused towards the GAL4 DNA-binding domains (GAL4-DB) in vector pAS2-1 (Clontech). This create was used as bait to display a Z-VAD-FMK inhibition human being lymphocyte cDNA library fused to a GAL4 activation website (GAL4-AD) in the pACT2 vector (Clontech). The two types of plasmids were then cotransformed into Y190, and the transformants were selected on SD minimal medium as previously explained (40). Positive colonies were further tested for -galactosidase activity using a colony-lift assay and liquid assay as explained by the manufacturer (Clontech). To thin down the head website region of 4.1R (4.1R-HD) that binds to CPAP, constructs containing numerous portions of 4.1R-HD were fused to GAL4-DB of the pAS2-1 vector (Fig. ?(Fig.1A).1A). The C terminus of CPAP ...
HEADER TRANSFERASE 08-JAN-07 2OGQ TITLE MOLECULAR AND STRUCTURAL BASIS OF PLK1 SUBSTRATE TITLE 2 RECOGNITION: IMPLICATIONS IN CENTROSOMAL LOCALIZATION COMPND MOL_ID: 1; COMPND 2 MOLECULE: SERINE/THREONINE-PROTEIN KINASE PLK1; COMPND 3 CHAIN: A; COMPND 4 FRAGMENT: POLO-BOX DOMAIN, RESIDUES 365-603; COMPND 5 SYNONYM: POLO-LIKE KINASE 1, PLK-1, SERINE/THREONINE- COMPND 6 PROTEIN KINASE 13, STPK13; COMPND 7 EC: 2.7.11.21; COMPND 8 ENGINEERED: YES SOURCE MOL_ID: 1; SOURCE 2 ORGANISM_SCIENTIFIC: HOMO SAPIENS; SOURCE 3 ORGANISM_COMMON: HUMAN; SOURCE 4 ORGANISM_TAXID: 9606; SOURCE 5 GENE: PLK1, PLK; SOURCE 6 EXPRESSION_SYSTEM: ESCHERICHIA COLI; SOURCE 7 EXPRESSION_SYSTEM_TAXID: 562; SOURCE 8 EXPRESSION_SYSTEM_STRAIN: BL21, ROSETTA; SOURCE 9 EXPRESSION_SYSTEM_VECTOR_TYPE: PLASMID; SOURCE 10 EXPRESSION_SYSTEM_PLASMID: PGEX-6P-2 KEYWDS POLO BOX DOMAIN, TRANSFERASE EXPDTA X-RAY DIFFRACTION AUTHOR B.GARCIA-ALVAREZ,G.DE CARCER,S.IBANEZ,E.BRAGADO-NILSSON, AUTHOR 2 G.MONTOYA REVDAT 3 24-FEB-09 2OGQ 1 VERSN ...
Complete information for CEP44 gene (Protein Coding), Centrosomal Protein 44, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Behavior, Cells, Laser, Microscopy, DNA, Ethanol, Light, Water, RNA, Animal, Centrioles, Centrosome, Centrosomes, Charge, Drosophila, Electron, Electron Microscopy, Electrons, Electrophoresis, Embryo
is critical for microtubule formation and degranulation and it may perform this function by trafficking adaptor molecules and kinases to the pericentrosomal and Golgi region in response to Ca2+ ...
Reagents, Tools and Custom Services for molecular biology, specializing in the fields of Nano-Antibody development (nAb), Cellular Reprogramming (iPSC), Genome Editing, Fluorescent Proteins, RNAi, Viral Packaging and Protein expression.
HAUS, the 8-subunit human Augmin complex, regulates centrosome and spindle integrity.. Current Biology Current Biology. 19:816-826. 2009 ...
Animal Cell The nucleus is a large organelle that is normally 5 micrometers in length and contains most of the genetic material of a cell. Centrosome A digestive organelle where macromolecules are hydrolyzed Lysosome Organelle active in synthesis, modification, sorting and secretion of cell products This is the membrane enclosing the cell, it is made of a bilayer of phospolipids that only allow some things into the cell This is a chromosome. Chromosomes are long strands of DNA that stay in pairs. The average cell contains 23 pairs of chromosomes. Chromosomes also determine the sex of a person. This is the Nuclear Envelope ...
Doxsey Laboratory is dedicated to understand the function of non-membranous organelles, the centrosomes and the midbody during cell division & ciliogenesis.
Complete information for CEP131 gene (Protein Coding), Centrosomal Protein 131, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
... : centripetally, centrism, centrist, centrobaric, centroclinal, centrode, centroid, centroidal, centroids, centrolecithal, centromere, centromeric, centrosome, centrosomic, centrosphere, centrosymmetric, centrum, centry, cents, centu...
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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 ...
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 ...
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
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
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. ...
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 ...
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 ...
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). ...
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 ...
... , 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 ...
In some patients with microcephaly, a neuronal disorder that leads to a reduced number of nerve cells being produced and, therefore, a smaller brain, the KEN-box is lacking from the STIL protein. The scientists were thus able to demonstrate a tantalizing connection between the absence of this particular amino acid signal and an illness. "When during our investigations of cell division and centrosome duplication we came across a connection to the disorder microcephaly, we were particularly pleased, as this helps us to better understand how this disorder develops," says Christian Arquint.. In the future, the research group led by Erich Nigg plans to uncover other connections between errors of cell division and the illness microcephaly. They also want to focus on the investigation of other proteins that play important roles in the process of cell division, in particular those involved in centrosome duplication.. Original Citation ...
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Colocalization experiments of Pfark-1-GFP with a-tubulin. Fluorescence microscopy of fixed schizont stage transgenic parasites expressing Pfark-1-GFP. A and B. An anti-a-tubulin mAb recognizes discrete foci (red) near DAPI-stained nuclear DNA (blue). The red fluorescent pattern is consistent with early-stage mitotic spindle formation developing from the spindle pole bodies anchored in the nuclear membrane. In colour merge images, the Pfark-1-GFP protein appears to localize at opposite sides of the early mitotic spindle, consistent with a localization at the mitotic spindle poles. C and D. In these two panels the anti-a-tubulin mAb recognizes partly disassembled bipolar mitotic spindles (red) aligned with DAPI-stained nuclear bodies (blue), representing daughter nuclear bodies in the process of completion of nuclear division. The Pfark-1-GFP protein does not appear now to be confined to mitotic spindle poles. A diffuse cytosolic green fluorescence is observable, presumably representing the GFP ...
Mammalian cells are capable of de novo centriole formation after the removal of existing centrioles. This suggests that de novo centriole assembly is repressed in normally duplicating cells to maintain a constant number of centrioles in the cells. However, neither the mechanism of de novo centriole assembly nor that of its hypothesized repression is understood due to the lack of an experimental system. We found that the heat shock (HS; 42°C, 2 h) of mouse embryonic fibroblasts caused the separation of centriole pairs, a transient increase in polo-like kinase (Plk) 4 expression, and the formation of a complex containing γ-tubulin, pericentrin, HS protein (Hsp) 90, and Plk4, in approximately half of the cells ...
We reported an updated database of MiCroKiTS 4.0 (http://microkit.biocuckoo.org) for proteins temporally and spatially localized in distinct subcellular positions including midbody, centrosome, kinetochore, telomere and mitotic spindle during cell division/mitosis. The database was updated from our previously developed database of MiCroKit 3.0, which contained 1489 proteins mostly forming super-complexes at midbody, centrosome and kinetochore from seven eukaryotes. Since the telomere and spindle apparatus are critical for cell division, the proteins localized at the two positions were also integrated. From the scientific literature, we curated 1872 experimentally identified proteins which at least locate in one of the five positions from eight species. Then the ortholog detection was performed to identify potential MiCroKiTS proteins from 144 eukaryotic organisms, which contains 66, 45 and 33 species of animals, fungi and plants, respectively. In total, 87,983 unique proteins with corresponding ...
Nek2 (NIMA-related kinase 2) is a cell cycle-dependent serine/threonine protein kinase that regulates centrosome separation at the onset of mitosis. Overexpression of Nek2 is common in human cancers and suppression can restrict tumor cell growth and promote apoptosis. Nek2 inhibition with small molecules, therefore, offers the prospect of a new therapy for cancer. To achieve this goal, a better understanding of the requirements for selective-inhibition of Nek2 is required. 6-Alkoxypurines were identified as ATP-competitive inhibitors of Nek2 and CDK2. Comparison with CDK2-inhibitor structures indicated that judicious modification of the 6-alkoxy and 2-arylamino substituents could achieve discrimination between Nek2 and CDK2. In this study, a library of 6-cyclohexylmethoxy-2-arylaminopurines bearing carboxamide, sulfonamide and urea substituents on the 2-arylamino ring was synthesized. Few of these compounds were selective for Nek2 over CDK2, with the best result being obtained for ...
Ive been reading up on centriole biogenesis and centrosome duplication - look for more posts from myself on topics such as this: Plk4-Induced Centriole Biogenesis in Human Cells [Dev Cell. 2007 Aug;13(2):190-202]. From the introduction: We have previously shown that overexpression of Plk4 in human cells causes the recruitment of electron-dense material onto the proximal…
gamma tubulin Antibody 66320-1-Ig has been identified with ELISA, IF, IHC, WB. 66320-1-Ig detected 48-55 kDa band in NCCIT, HepG2, HSCT6, NIH/3T3 cell with 1:1000-1:8000 dilution...
EB3 Binds to the plus end of microtubules and regulates the dynamics of the microtubule cytoskeleton. Promotes microtubule growth. May be involved in spindle function by stabilizing microtubules and anchoring them at centrosomes. May play a role in cell migration. Belongs to the MAPRE family. 2 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB ...
Xenopus Eg2 protein: associates with the centrosome in a cell cycle-dependent manner, binds to the spindle microtubules & is involved in the bipolar mitotic spindle assembly; MW 46 kDa; GenBank Z17207
Background Required for normal spindle assembly. Plays a key role in mother-centriole-dependent centriole duplication, through centrosomal recruitment of CEP152. Also recruits CDK1 to centrosomes. Plays a role in DNA damage...
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This entry represents a C-terminal domain found in members of the T complex protein 10 family. This domain contains unusual G repeats [(PUBMED:11003675)]. Centromere protein J, a member of the TCP10 family, inhibits microtubule nucleation from the centrosome and depolymerises taxol-stabilised microtubules [(PUBMED:12068715)]. T-complex is involved in spermatogenesis in mice [(PUBMED:15047868 ...
This gene encodes a centrosomal protein which regulates centriole amplification by limiting centriole duplication to once per cell cycle. Alternative splicing results in multiple transcript variants ...
In our lab we are using a combination of biochemical, cell biological and genetic approaches in the nematode C. elegans to investigate the fundamental and conserved molecular mechanisms underlying centriole assembly and function. In previous work we have taken advantage of the availability of data from genome-wide RNAi-based screens to define the molecular requirements for centriole assembly. The six-protein molecular pathway we identified has since been found to be conserved from ciliates to vertebrates, and is thought to form the core of the centriole assembly machinery in all eukaryotes. We further identified the hydrolethalus syndrome protein HYLS-1 as a core centriolar protein that is incorporated into centrioles during their assembly to confer on them the ability to initiate cilia. The single amino acid missense mutation associated with hydrolethalus syndrome impairs HYLS-1 function in ciliogenesis, identifying this disorder as a severe (perinatal lethal) ciliopathy ...
The blockbuster chemotherapy drug paclitaxel is widely presumed to cause cell death in tumors as a consequence of mitotic arrest, as it does at concentrations routinely used in cell culture. However, we determine here that paclitaxel levels in primary breast tumors are well below those required to elicit sustained mitotic arrest. Instead, cells in these lower concentrations of drug proceed through mitosis without substantial delay and divide their chromosomes on multipolar spindles, resulting in chromosome missegregation and cell death. Consistent with these cell culture data, most mitotic cells in primary human breast cancers contain multipolar spindles after paclitaxel treatment. Contrary to the previous hypothesis, we find that mitotic arrest is dispensable for tumor regression in patients. These results demonstrate that mitotic arrest is not responsible for the efficacy of paclitaxel, which occurs because of chromosome missegregation on highly abnormal, multipolar spindles. This mechanistic ...
Centrioles are microtubule-based organelles crucial for cell division, sensing and motility. In Caenorhabditis elegans, the onset of centriole formation requires notably the proteins SAS-5 and SAS-6, which have functional equivalents across eukaryotic evolution. Whereas the molecular architecture of SAS-6 and its role in initiating centriole formation are well understood, the mechanisms by which SAS-5 and its relatives function is unclear. Here, we combine biophysical and structural analysis to uncover the architecture of SAS-5 and examine its functional implications in vivo. Our work reveals that two distinct self-associating domains are necessary to form higher-order oligomers of SAS-5: a trimeric coiled coil and a novel globular dimeric Implico domain. Disruption of either domain leads to centriole duplication failure in worm embryos, indicating that large SAS-5 assemblies are necessary for function in vivo. Rogala, Kacper B; Dynes, Nicola J; Hatzopoulos, Georgios N; Yan, Jun; Pong, Sheng Kai;
RanGTP is important for chromosome-dependent spindle assembly in Xenopus extracts. Here we report on experiments to determine the role of the Ran pathway on microtubule dynamics in Drosophila oocytes and embryos. Females expressing a dominant-negative form of Ran have fertility defects, suggesting that RanGTP is required for normal fertility. This is not, however, because of a defect in acentrosomal meiotic spindle assembly. Therefore, RanGTP does not appear to be essential or sufficient for the formation of the acentrosomal spindle. Instead, the most important function of the Ran pathway in spindle assembly appears to be in the tapering of microtubules at the spindle poles, which might be through regulation of proteins such as TACC and the HURP homolog, Mars. One consequence of this spindle organization defect is an increase in the nondisjunction of achiasmate chromosomes. However, the meiotic defects are not severe enough to cause the decreased fertility. Reductions in fertility occur because ...
Cytolytic cells of the immune system destroy pathogen-infected cells by polarised exocytosis of secretory lysosomes containing the pore-forming protein perforin. Precise delivery of this lethal hit is essential to ensuring that only the target cell is destroyed. In cytotoxic T lymphocytes (CTLs), this is accomplished by an unusual movement of the centrosome to contact the plasma membrane at the centre of the immunological synapse formed between killer and target cells. Secretory lysosomes are directed towards the centrosome along microtubules and delivered precisely to the point of target cell recognition within the immunological synapse, identified by the centrosome. We asked whether this mechanism of directing secretory lysosome release is unique to CTL or whether natural killer (NK) and invariant NKT (iNKT) cytolytic cells of the innate immune system use a similar mechanism to focus perforin-bearing lysosome release. NK cells were conjugated with B-cell targets lacking major histocompatibility
TY - JOUR. T1 - The Drosophila pericentrin-like protein is essential for cilia/flagella function, but appears to be dispensable for mitosis. AU - Martinez-Campos, Maruxa. AU - Basto, Renata. AU - Baker, James. AU - Kernan, Maurice. AU - Raff, Jordan W.. PY - 2004/6/7. Y1 - 2004/6/7. N2 - Centrosomes consist of a pair of centrioles surrounded by an amorphous pericentriolar material (PCM). Proteins that contain a Pericentrin/AKAP450 centrosomal targeting (PACT) domain have been implicated in recruiting several proteins to the PCM. We show that the only PACT domain protein in Drosophila (the Drosophila pericentrin-like protein [D-PLP]) is associated with both the centrioles and the PCM, and is essential for the efficient centrosomal recruitment of all six PCM components that we tested. Surprisingly, however, all six PCM components are eventually recruited to centrosomes during mitosis in d-plp mutant cells, and mitosis is not dramatically perturbed. Although viable, d-plp mutant flies are severely ...
Microtubules are an essential feature of eukaryotic cells as they divide, change shape, and transport organelles. Microtubule-associated proteins (MAPs) play crucial roles in organizing microtubules. MICROTUBULE ORGANIZATION 1 (MOR1) of Arabidopsis (Arabidopsis thaliana) belongs to the MAP215/Dis1 family of MAPs (Whittington et al., 2001), a highly conserved group of MAPs found in all eukaryotes examined to date (Gard et al., 2004). MOR1 was initially discovered through the isolation of two mutants that both undergo temperature-dependent cortical microtubule disorganization, which leads to the left-handed twisting and eventual radial swelling of organs. Both mutations substitute single amino acids (mor1-1L174F and mor1-2E195K) in an N-terminal HEAT repeat, one of many such motifs found extensively along the length of MOR1 and other MAP215/Dis1 family proteins (Whittington et al., 2001). Another mor1 allele, rid5, has a similar morphological phenotype to the mor1 mutants. The rid5 mutation has a ...
Aurora kinases play distinct roles during mitosis, with Aurora A being essential for centrosome maturation and spindle assembly and Aurora B functioning at kinetochores in chromosome attachment and at the end of mitosis in cytokinesis (reviewed in refs. 3, 4).. Inhibition of Aurora kinases is emerging as a new strategy for anticancer therapy, and several small-molecule inhibitors have entered clinical trials. In this report, we describe the biochemical and pharmacologic activity profile of PHA-739358, a spectrum-selective small-molecule kinase inhibitor, which was identified during a screen for inhibitors of Aurora kinases. In most of the cell lines tested, cells fail to divide, resulting in polyploidy without a strong impact on the timing of mitosis (data not shown) and finally leading to a reduction in viability. In some cell lines, an increased apoptosis was seen. This speaks for a dominant Aurora B kinase-related mechanism of action for inhibition because Aurora A inhibition would rather ...

CEP250 elisa kit | Canine Centrosome-associated protein CEP250 (CEP250) ELISA Kit-NP 009117.2CEP250 elisa kit | Canine Centrosome-associated protein CEP250 (CEP250) ELISA Kit-NP 009117.2

Canine Centrosome-associated protein CEP250 (CEP250) ELISA Kit-NP_009117.2 (MBS7251685) product datasheet at MyBioSource, ELISA ... Centrosome-associated protein CEP250 (CEP250), ELISA Kit. Also Known As Canine Centrosome-associated protein CEP250 (CEP250) ... Centrosome Maturation Pathway antibodies. Centrosome Maturation Pathway Diagram. G2/M Transition Pathway antibodies. G2/M ... Recruitment Of Mitotic Centrosome Proteins And Complexes Pathway antibodies. Recruitment Of Mitotic Centrosome Proteins And ...
more infohttps://www.mybiosource.com/prods/ELISA-Kit/Canine/Centrosome-associated-protein-CEP250-CEP250/CEP250/datasheet.php?products_id=7251685

The Origin of the Second Centriole in the Zygote of Drosophila melanogaster | GeneticsThe Origin of the Second Centriole in the Zygote of Drosophila melanogaster | Genetics

1994 The centrosome and its mode of inheritance: the reduction of the centrosome during gametogenesis and its restoration ... PCL and GC undergo centrosome reduction during late spermiogenesis. At the end of spermiogenesis, mammalian centrosomes undergo ... the sperm and the oocyte modify or lose their centrosomes. Consequently, how the zygote establishes its first centrosome, and ... and becoming the primary centrosome (Delattre and Gonczy 2004). This centrosome, in the zygote, acts as a microtubule- ...
more infohttps://www.genetics.org/node/342293.full.print

Biology-Online • View topic - function of a centriole?Biology-Online • View topic - function of a centriole?

Within the centrosomes, the two centrioles are positioned in such a way that both are perpendicular to each other. Like other ... centrosome is the region where the centriolles are contained. note: its the region. you could use a dictionary ... In other words, the centrioles are found within the centrosomes, which is a small region in the cytoplasm near the nucleus. ... two centrioles form one centrosome. Function - forms spindle fibres to separate chromosomes during cell. division. ...
more infohttp://www.biology-online.org/biology-forum/about2964.html?p=132983&hilit=Spindles

Centriole Biogenesis: Polo-like Kinase as a vital factor? | MigrationsCentriole Biogenesis: Polo-like Kinase as a vital factor? | Migrations

Ive been reading up on centriole biogenesis and centrosome duplication - look for more posts from myself on topics such as ... 30th, 2007 by Dan A week ago, I mentioned Plk4 as a kinase implicated in centrosome duplication. An array of other factors ... In any case, look for more discussions from me on papers of other proteins potentially involved in centrosome duplication! That ... Ive been reading up on centriole biogenesis and centrosome duplication - look for more posts from myself on topics such as ...
more infohttps://migration.wordpress.com/2007/08/23/centriole-biogenesis-polo-like-kinase-as-a-vital-factor/

B4J3F1 | SAK | Serine/threonine-protein kinase PLK4 | Druggability | CancerB4J3F1 | SAK | Serine/threonine-protein kinase PLK4 | Druggability | Cancer

Centrosome amplification following overexpression can initiate tumorigenesis, highlighting the importance of centrosome ... it is able to induce centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each ... Centrosome amplification following overexpression can initiate tumorigenesis, highlighting the importance of centrosome ... it is able to induce centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each ...
more infohttps://cansarblack.icr.ac.uk/target/B4J3F1/synopsis

Centriole assembly and function - DK Chromosome DynamicsCentriole assembly and function - DK Chromosome Dynamics

Centrosome and cilia abnormalities have been linked to aneuploidy and tumorigenesis as well as developmental disorders ... Centrioles perform two distinct functions in eukaryotic cells: 1) they recruit pericentriolar material to form centrosomes that ... how do centrioles recruit pericentriolar material to form centrosomes and what is the molecular nature of this material; and 3 ...
more infohttp://gscd.gmi.oeaw.ac.at/Plone/topics/centriole-assembly-and-function-group-dammermann

centrosome | IRB Barcelonacentrosome | IRB Barcelona

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 ...
more infohttps://www.irbbarcelona.org/en/tags/centrosome

Centrosome misorientation reduces stem cell division during ageing | NatureCentrosome misorientation reduces stem cell division during ageing | Nature

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) ...
more infohttps://www.nature.com/articles/nature07386?error=cookies_not_supported&code=502535e9-0b8c-42a9-a63e-acf3aeb9d1af

Sorting Out the Centrosome | Science SignalingSorting Out the Centrosome | Science Signaling

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. ...
more infohttp://stke.sciencemag.org/content/4/179/ec179

Centrosome - WikipediaCentrosome - Wikipedia

The centrosome is thought to have evolved only in the metazoan lineage of eukaryotic cells. Fungi and plants lack centrosomes ... 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 structures ... Unlike centrioles, centrosomes are required for survival of the organism. Cells without centrosomes lack radial arrays of ...
more infohttps://en.wikipedia.org/wiki/Centrosome

Centrosome - Simple English Wikipedia, the free encyclopediaCentrosome - Simple English Wikipedia, the free encyclopedia

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. ...
more infohttps://simple.wikipedia.org/wiki/Centrosome

The Centrosome (ebook) by Heide Schatten | 9781627030359The Centrosome (ebook) by Heide Schatten | 9781627030359

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 ...
more infohttps://www.ebooks.com/994635/the-centrosome/schatten-heide/

Centrosome facts, information, pictures | Encyclopedia.com articles about CentrosomeCentrosome facts, information, pictures | Encyclopedia.com articles about Centrosome

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 ...
more infohttps://www.encyclopedia.com/plants-and-animals/zoology-and-veterinary-medicine/zoology-general/centrosome

Centrosome amplification, chromosome instability and cancer development.  - PubMed - NCBICentrosome amplification, chromosome instability and cancer development. - PubMed - NCBI

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 ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/16253756?dopt=Abstract

Polar expeditions--provisioning the centrosome for mitosis.  - PubMed - NCBIPolar expeditions--provisioning the centrosome for mitosis. - PubMed - NCBI

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. ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/12776127?dopt=Abstract

Centrosome cycle - WikipediaCentrosome cycle - Wikipedia

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, so that by the time mitosis occurs there are two centrosomes ... The centrosome cycle is important to ensure that daughter cells receive a centrosome after cell division. As the cell cycle ... Centrosomes are the major microtubule organizing center (MTOC) in mammalian cells. Failure of centrosome regulation can cause ...
more infohttps://en.wikipedia.org/wiki/Centrosome_cycle

Centrosome Loss in the Evolution of Planarians | ScienceCentrosome Loss in the Evolution of Planarians | Science

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 ...
more infohttp://science.sciencemag.org/content/early/2012/01/04/science.1214457

Results for Centrosome | Abcam: antibodies, proteins, kits...Results for 'Centrosome' | Abcam: antibodies, proteins, kits...

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) ...
more infohttps://www.abcam.com/products?selected.researchAreas=Tags+%26+Cell+Markers--Subcellular+Markers--Organelles--Centrosome

Quiz & Worksheet - Centrosome | Study.comQuiz & Worksheet - Centrosome | Study.com

Centrosomes and their functions within a cell are reviewed within this interactive quiz. To keep this information available at ... You can learn more about centrosomes by studying the lesson that focuses on them, titled Centrosomes: Definition & Function. ... This quiz will let you gauge how much you know about centrosomes, their structure, and their role in a cell. You will complete ... Reading comprehension - ensure that you draw the most important information from the related lesson about centrosomes ...
more infohttps://study.com/academy/practice/quiz-worksheet-centrosome.html

Link Unraveled Between Chromosomal Instability, Centrosome Defects In Cancer Cells - RedorbitLink Unraveled Between Chromosomal Instability, Centrosome Defects In Cancer Cells - Redorbit

"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 ...
more infohttp://www.redorbit.com/news/health/1701466/link_unraveled_between_chromosomal_instability_centrosome_defects_in_cancer_cells/

Centrosome amplification may contribute to initiation of cancers, research suggestsCentrosome amplification may contribute to initiation of cancers, research suggests

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 ...
more infohttps://www.news-medical.net/news/20180508/Centrosome-amplification-may-contribute-to-initiation-of-cancers-research-suggests.aspx

The Centrosome in Cell Replication and Early Development - Google BooksThe Centrosome in Cell Replication and Early Development - Google Books

... 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. ...
more infohttps://books.google.ca/books?id=QzuEZI6PP8QC&printsec=frontcover

The Centrosome in Cell Replication and Early Development - Google BooksThe Centrosome in Cell Replication and Early Development - Google Books

... 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. ...
more infohttps://books.google.ca/books?id=QzuEZI6PP8QC&printsec=frontcover&source=gbs_ge_summary_r&cad=0

SADB kinases license centrosome replicationSADB kinases license centrosome replication

... Carrera, Ana and Alvarado-Kristensson, Maria LU (2009) In Cell Cycle 8(24). p.4005 ... progression, cell cycle, gamma-tubulin, phosphorylation, SadB, centrosomes. in Cell Cycle. volume. 8. issue. 24. pages. 4005 - ... centrosomes}, language = {eng}, number = {24}, pages = {4005--4006}, publisher = {Landes Bioscience}, series = {Cell Cycle}, ...
more infohttps://lup.lub.lu.se/search/publication/1531742
  • 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 ). (genetics.org)
  • 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)
  • 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)
  • 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)
  • 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)
  • The Role of the Centrosome in the Development of Malignant Tumors, W.L. Lingle and J.L. Salisbury . (elsevier.com)
  • Centrosome alterations in cancer can be divided in two subgroups, structural or numeric aberrations, yet both can be simultaneously found in a tumor. (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)
  • 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)
  • 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)
  • 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)
  • Regulating Centrosomes by Protein Phosphorylation, A.M. Fry, T. Mayor, and E.A. Nigg . (elsevier.com)
  • Nucleophosmin is only found in unreplicated centrosomes and it's phosphorylation by Cdk2/cyclin E removes NPM from the centrosomes, initiating procentriole formation. (wikipedia.org)
  • Phosphorylation is a key regulatory role in centrosome maturation and it is thought that Polo-like kinases (Plks) and Aurora kinases are responsible for this phosphorylation. (wikipedia.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)
  • The C. elegans centrosome during early embryonic development. (worldcat.org)
  • Cells with more than two centrosomes enter a "multipolar" phase with several axes along which division may take place. (redorbit.com)
  • The theme issue is enriched by a unique contribution on Theodor Boveri, who pioneered work on the centrosome well over a century ago. (royalsocietypublishing.org)
  • 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)
  • Our study uncovers the molecular architecture and evolution of the animal centrosome and emphasizes the plasticity of animal cell biology and development. (sciencemag.org)
  • Volume 49 of Current Topics in Developmental Biology will present all known research surrounding the centrosome, across a variety of systems, will be well referenced, and speculate where the research is headed. (elsevier.com)
  • The study of the centrosome is a very ancient field of cell biology that has regained substantial interest in recent years. (royalsocietypublishing.org)
  • 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: 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)
  • Moreover, the numerous functions of the centrosome, including at the immunological synapse and as signalling centres, are discussed. (royalsocietypublishing.org)
  • Using Centrosome Fragments in the Directed Assembly of Microtubul. (ingentaconnect.com)
  • In the study reported here, we examine microtubule dynamics within the centrosome-free fragments and find that, after severing, microtubule reorganization is initiated at the proximal (cut) end of an arm and migrates distally with the aggregated pigment mass until it becomes permanently positioned at the middle of the arm. (rupress.org)