mitotic spindle apparatus

..Thus, our data confirm an important role of Plk1 in bipolar spindle formation, and also demonstrate that Plk1 is dispensable for APC/C-Cdc20 activation and the initiation of cytokinesis...

..Our integrated analysis predicts that up to 97 new centromere-associated proteins remain to be discovered in our data set...

..This review will focus on how interacting proteins make this functional diversity possible by targeting the kinases to different subcellular locations and regulating their activity...

..These findings provide a direct mechanistic link between extra centrosomes and CIN, two common characteristics of solid tumours. We propose that this mechanism may be a common underlying cause of CIN in human cancer...

..The normal apical exclusion of LGN during mitosis appears to be mediated by atypical PKC. Thus, cell polarization-mediated spatial restriction of spindle orientation determinants is critical for epithelial morphogenesis...

..We show here that attempts of cytokinesis in these oocytes abort due to phospho-myosin II mislocalization...

..Thus, control of symmetric division, essential for neuroepithelial stem cell proliferation, is mediated through spindle orientation determined via LIS1/NDEL1/dynein-mediated cortical microtubule capture...

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..Lessons learned from these two model organisms also apply to cells that divide asymmetrically in other metazoans, such as self-renewing stem cells in mammals...

..Our results reveal that sliding forces at the midzone are activated by separase and explain how spindle elongation is triggered with anaphase entry...

..We propose this spindle pole coalescence mechanism as a major contributor to chromosome instability in cancer cells...

..Loss of stiffness caused by condensin-depletion produces abnormal uncoordinated sister kinetochore movements, leads to an increase in Mad2(+) kinetochores near the metaphase plate and delays anaphase onset...

..Mps1 phosphorylation of Cdc31 at the conserved T110 residue controls substrate binding to Kar1 protein. These findings explain the multiple SPB duplication defects of mps1 mutants on a molecular level...

..Further, the yeast homolog of hPaf1 has a role in regulating the expression of a subset of genes involved in the cell-cycle. We therefore investigated the role of hPaf1 during progression of the cell-cycle...

..In turn, asymmetric distribution of Kar9 ensures that only one pole orients toward the bud. Our results indicate that Cdk1-dependent spindle asymmetry ensures proper alignment of the mitotic spindle with the cell division axis...

..Taken together, these data reveal a specific role for pericentromeric linkage in ensuring kinetochore biorientation...

..Here, we review recent studies that uncover new players and provide a greater understanding of the regulation of centrosome (or SPB) separation...

..As a result, the technique described herein may be used as a biophysical strategy to probe the intranuclear environment...

..Finally, a stable barrel-shaped acentrosomal metaphase spindle with oscillating chromosomes and astral-like microtubules forms that surprisingly exhibits key properties of a centrosomal spindle...

..Together, these studies reinforce the notion that limiting gamma-tubulin availability during meiotic maturation ensures coordination of karyokinesis and cytokinesis and conservation of gamma-tubulin as an embryonic reserve...

..These data indicate that Ric-8A signaling leads to assembly of a cortical signaling complex that functions to orient the mitotic spindle...

..These data have uncovered two important regulatory points controlling ACD in the epidermis and allow a framework for analysis of how external cues control this important choice...

..Defects in signaling through Cdc42 and atypical protein kinase C (aPKC) also cause spindle misorientation. When epithelial cysts are grown in 3D cultures, misorientation creates multiple lumens...

..We then discuss models for force integration and spindle length determination. We also emphasize key missing data that notably include absolute values of forces and how they vary as a function of position within the spindle...

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..We suggest that this network plays a major role in silencing the spindle checkpoint when chromosomes are aligned at metaphase to allow timely anaphase onset and mitotic exit...

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..Such a mechanism may help restrict new centriole assembly to the vicinity of preexisting parent centrioles that recruit PCM...

..Our findings indicate that CKIdelta plays an important role in the mitotic progression and in the survival of cells of trophoblast origin. Therefore, IC261 could provide a new tool in treating choriocarcinomas...

..Here we review some recent developments involving Drosophila and mammalian neural progenitor cells, highlighting some similarities and differences in the mechanisms that regulate their divisions during neurogenesis...

..We suggest that Nudel regulates microtubule organization in part by facilitating assembly of the lamin B spindle matrix in a dynein-dependent manner...

..In sum, Top2 seems to play a novel role in CEN compaction that is distinct from decatenation. Perturbations to this function may allow weakened kinetochores to stretch CENs in a manner that mimics tension or evades Ipl1 surveillance...

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..Based on these results, we propose the first mechanistic model for asymmetric spindle positioning in mammalian oocytes and validate five of its key predictions experimentally...

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..We propose that an early Lis1/dynactin-dependent pathway and a late Lis1/dynactin-independent pathway regulate neuroblast spindle orientation...

..These findings have direct implications for proliferative tissue homeostasis as well as for cellular and organismal aging...

..In conclusion, when all kinetochores lack attachment and tension, mouse oocytes mount a robust Mad2-dependent meiosis I arrest which inhibits the destruction of securin and cyclin B...

..The Inscuteable protein localizes to the apical cell cortex before mitosis, suggesting that Inscuteable functions in establishing polarity for asymmetric cell division...

..In addition, cell cycle arrest and survival of tub4-1 cells is dependent on the mitotic checkpoint control gene BUB2 (Hoyt, M.A., L. Totis, B.T. Roberts. 1991. Cell. 66:507-517), one of the cell's monitors of spindle integrity...

..Here, we discuss different pathways that promote initial centrosome separation and bipolar spindle assembly...

..Taken together, these results suggest that Aurora A inhibition kills tumor cells through the development of deleterious aneuploidy...

..Combinatorial inhibition of these subprocesses yielded cells with hyperstable spindle remnants and dramatic defects in cell cycle progression, establishing that rapid spindle disassembly is crucial for cell proliferation...

..Understanding these mechanisms may lead to the discovery of new and improved anticancer therapies...

..The kinase Mps1p, which functions in SPB duplication and mitotic checkpoint control, seems to be involved in Spc98p phosphorylation. Our results also suggest that the nuclear and cytoplasmic Tub4p complexes are regulated differently...

..Our results suggest that Sli15(INCENP) dephosphorylation is part of an evolutionarily conserved mechanism that prevents the mitotic checkpoint from reengaging when tension between sister chromatids is lost at anaphase onset...

..We discuss how tension-sensitive phenomena, such as attachment correction and stabilization, relate to the SAC and we speculate on the existence of a single pathway linking error correction and SAC activation...

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..It is currently unclear whether kinetochores control and coordinate the dynamics of individual kinetochore microtubules...

..But when it comes to packaging and segregating a genome, the mechanisms are only beginning to be understood and are often as variable as the organisms in which they are studied...

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..In this review, we will discuss this evolving area of study and emerging hypotheses that propose key roles for components of the nuclear transport apparatus in mitotic progression...

..Thus, a topological change on DNA drives topoisomerase II to decatenate molecules during mitosis, potentially driving the full decatenation of the genome...

..Based on these findings, we propose that Clb/Cdc28 drives spindle pole separation by direct phosphorylation of kinesin-5 motors...

..The results confirm Bub3 as a component of the essential spindle checkpoint pathway that operates during early embryogenesis...

..Taken together, our results constitute a large quantitative data resource of phosphorylation abundances at distinct mitotic stages and they provide insight into the systems properties of phosphorylation dynamics during mitosis...

..Thus, CLASP1-astrin-Kif2b complex act as a central switch at kinetochores that defines mitotic progression and promotes fidelity by temporally regulating kMT attachments...

..These results indicate that spindle rotation is essential for polar body extrusion; it is the microfilaments that play a crucial role in regulating rotation of the meiotic spindle...

..We propose that the dual detection of chromosomes and microtubules by the CPC is a critical step in assembling spindles around and only around chromosomes...

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..These studies are the first to employ proteomics analyses coupled to functional interventions to rescue a specific molecular defect in cloned embryos...

..The kip3Delta and kip1Delta mutants affect the duration of anaphase, but cin8Delta does not...

..They also shed light on the relationship between the error correction pathway and the spindle checkpoint and suggest that these processes are coregulated and are likely to share at least a subset of their catalytic machinery...

..We propose that Msd1 interacts with gamma-TuC, thereby specifically anchoring the minus end of microtubules to SPBs without affecting microtubule nucleation...

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..These data support a modified search-and-capture model that incorporates additional assembly pathways coordinated by a RanGTP gradient...

..In summary, this study has extended our previous study of Mars in cell cycle regulation and provided further evidence showing that Mars is required for the assembly of kinetochore microtubules...

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..Because gamma-TuRC inhibition leads to pleiotropic spindle defects, which are well known to activate kinetochore-derived checkpoint signaling, we believe that this conclusion is premature...

..Overall our results suggest that activation of the mechanism that corrects inappropriate kinetochore attachment requires the antagonistic effects of BubR1 and CENP-E...

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..These data indicate that Klp5p and Klp6p are kinetochore kinesins required for normal chromosome movement in prometaphase...

..This provides a novel mechanism for dysregulation of the mitotic checkpoint by a viral pathogen linking it to the accumulation of chromosomal instability in HBV-associated hepatocarcinogenesis...

..Thus, in prometaphase, dynein/dynactin likely mediates early transient, lateral interactions of kinetochores and microtubules. However, mature attachment via the Ndc80 complex is essential for metaphase alignment and anaphase A...

..A recent study describes a novel role for the centrosomal protein Cep57 in attaching spindle microtubules to both kinetochores and centrosomes, suggesting similar mechanisms may be used for generating these two distinct linkages in mitosis...

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..We suggest that astrin contributes to the regulatory network that controls separase activity...

..We propose that NEK2A-mediated phosphorylation of human Sgo1 provides a link between centromeric cohesion and spindle microtubule attachment at the kinetochores...

..At the metaphase-anaphase transition, cohesion between sister chromatids is removed, and each sister chromatid is pulled to opposite poles of the cell by microtubule-dependent forces...

..The screen, in combination with a variety of secondary assays, led to new insights into how spindle microtubules are generated; how centrosomes are positioned; and how centrioles, centrosomes, and kinetochores are assembled...

..Activation of Cdc14 by separase was sufficient for Sli15 dephosphorylation and relocalization. Cdc14 not only regulates mitotic exit but also modulates spindle midzone assembly through Sli15-Ipl1...

..Unlike conventional kinesins, members of the Kin I family are microtubule-depolymerizing enzymes, which are expected to be molecules that could generate poleward forces...

..We suggest that the coordination of chromosome movement and biorientation makes the kinetochore an autonomous segregation unit...

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..Thus, we have generated a comprehensive list of major mitotic microtubule-associated proteins, among which is astrin, a nonmotor spindle protein...

..We propose that cytosolic Mad2-BubR1 is essential to restrain anaphase onset early in mitosis when kinetochores are still assembling...

..Overall, we provide evidence that Stu2p promotes the dynamics of microtubule plus-ends in vivo and that these dynamics are critical for microtubule interactions with kinetochores and cortical sites in the cytoplasm...

..These phenotypes suggest that these proteins, and by extension their reorganization during mitosis, are important for mediating the checkpoint response as well as directing the assembly of the metaphase plate...

..We propose that the forces positioning the mitotic spindle asymmetrically are tethered until after the time of spindle assembly and that these same forces are used later to drive chromosome segregation at anaphase...

..These functions of the FEAR network contribute to genomic stability by coordinating the completion of anaphase and the execution of mitotic exit...

..Together, these results strongly support the conclusion that MAST/Orbit is required for microtubules to form functional attachments to kinetochores and to maintain spindle bipolarity...

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..The increase in microtubule ratio to opposite poles is the groundwork for a second mechanism, active in anaphase, that promotes the segregation of merotelically oriented chromosomes to the correct pole...

..Together, our data suggest that Aurora B is required to generate unattached kinetochores on monooriented chromosomes, which in turn could promote bipolar attachment as well as maintain checkpoint signaling...

..We propose that GSK-3 is regulated in a temporal and spatial manner during mitosis and, through controlling microtubule dynamics, plays an important role in chromosomal alignment on the metaphase plate...

..Thus, hSPC25 is an essential kinetochore component that plays a significant role in proper execution of mitotic events...

..Therefore, the checkpoint proteins form a complex intracellular signalling network to inhibit the anaphase-promoting complex...

..Simultaneous depletion of Hec1 and Mad2 caused catastrophic mitotic exit, making Hec1 an attractive target for the selective elimination of spindle checkpoint-deficient cells...

..It is further described how Drosophila mutants are used to address the functional interrelationships between individual centrosomal proteins and spindle formation in vivo...

..These results indicate that Scc1 is essential for the association of kinetochores with microtubules...

..Furthermore, molecular dissection of ZEN-4 will enhance our understanding of the mechanism of action of microtubule motors. ..

Microtubules are essential for many vital cellular processes, including formation of the mitotic spindle apparatus. The goal of our research is to identify and characterize molecular components of spindle poles, the organizing centers ..

..that delays the segregation of sister chromatids until all chromosomes are properly attached to the mitotic spindle apparatus and aligned at the metaphase plate...

..molecular machine that blocks the onset of anaphase until all chromosomes are properly attached to the mitotic spindle apparatus and aligned at the metaphase plate...

..aneuploidy by delaying sister chromatid separation until all chromosomes are properly attached to the mitotic spindle apparatus and aligned at the metaphase plate...

..2. Determine the role MAPK plays in regulating the formation and function of the mitotic spindle apparatus. 3. Determine the biochemical steps that regulate MAPK activation during mitosis...

..a cell prior to the metaphase to anaphase transition if all the chromosomes are not attached to the mitotic spindle apparatus. The main goal of the research being proposed is to determine if complete or partial loss of Mad2 ..

..a cell prior to the metaphase to anaphase transition if all the chromosomes are not attached to the mitotic spindle apparatus. Partial loss of function mutations predisposes mammalian cells to chromosome missegregation events and ..

..a cell prior to the metaphase to anaphase transition if all the chromosomes are not attached to the mitotic spindle apparatus. Partial loss of function mutations predisposes mammalian cells to chromosome missegregation events and ..

..conserved mitotic regulatory system that arrests cells when chromosomes are not properly aligned on the mitotic spindle apparatus. Mutations in spindle checkpoint genes have been implicated in genomic instability and tumor progression ..

..In particular, we are studying how the movement of the mitotic spindle apparatus and expression of fate determining molecules combine to allow for the switch between symmetrical and ..

..abstract_text> ..

..This Core will maintain the instrument and provide technical support to those Principal Investigators/Program Directors who are in need of low-light high- resolution 3-D fluorescent imaging. ..

..Since centrosome abnormalities are a hallmark of malignant tumors, the knowledge obtained in these studies will be useful for designing new strategies for the treatment of cancers. ..

..Newly discovered and conserved loci will also be studied in C. elegans and Drosophila. ..

..abstract_text> ..

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..Functional consequences of aberrant PKC signaling will be determined by observing the turning response of growth cones from DRG neurons expressing a dominant-negative, phosphorylation-deficient MARCKS mutant. ..

..Furthermore, molecular dissection of ZEN-4 will enhance our understanding of the mechanism of action of microtubule motors. ..

..Furthermore, molecular dissection of ZEN-4 will enhance our understanding of the mechanism of action of microtubule motors. ..

..An understanding of how this process occurs normally should provide insights into the molecular etiology of these diseases and suggest therapeutic strategies for their treatment. ..

..These studies will also have direct implications for understanding cancer causation, and applications in gene therapy. ..

..abstract_text> ..

..Finally, we will study the effects of these agents on cell proliferation, and apoptosis during different stages of colon carcinogenesis. ..

..We will focus on defining molecular mechanisms for these processes and understanding how they are regulated. ..