5,488 results match your criteria spindle assembly

Cytoskeletal biophysics: Passive crosslinker adapts to keep microtubule bundles on track.

Curr Biol 2021 Jun;31(12):R793-R796

Department of Physics, Cluster for Quantitative and Computational Developmental Biology, North Carolina State University, Raleigh, NC 27607, USA. Electronic address:

Assembly of the mitotic spindle requires dynamic adaptation and coordination among an array of motors and crosslinkers. A new study demonstrates in vitro how the mitotic crosslinker PRC1 can tune its behavior to regulate the speed of microtubule sliding. Read More

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Condensation of pericentrin proteins in human cells illuminates phase separation in centrosome assembly.

J Cell Sci 2021 Jun 22. Epub 2021 Jun 22.

Department of Cell Biology and Human Anatomy, University of California, Davis, School of Medicine, Davis, CA 95616, USA.

At the onset of mitosis, centrosomes expand the pericentriolar material (PCM) to maximize their microtubule-organizing activity. This step, termed centrosome maturation, ensures proper spindle organization and faithful chromosome segregation. However, as the centrosome expands, how PCM proteins are recruited and held together without membrane enclosure remains elusive. Read More

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Loss of aMTOCs disrupts spindle pole Aurora A and assembly of the liquid-like meiotic spindle domain (LISD) in oocytes.

J Cell Sci 2021 Jun 21. Epub 2021 Jun 21.

Department of Physiology and Pharmacology, College of Veterinary Medicine, GA, 30602, USA.

Oocyte-specific Pericentrin (PCNT) knockdown in transgenic (Tg) mice disrupts acentriolar microtubule organizing center (aMTOC) formation, leading to spindle instability and error-prone meiotic division. Here, we show that PCNT-depleted oocytes lack phosphorylated Aurora A (pAURKA) at spindle poles, while overall levels are unaltered. To test aMTOC-associated AURKA function, MII control (WT) and Tg oocytes were briefly exposed to a specific inhibitor (MLN8237). Read More

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Xenopus laevis Egg Extract Preparation and Live Imaging Methods for Visualizing Dynamic Cytoplasmic Organization.

J Vis Exp 2021 Jun 6(172). Epub 2021 Jun 6.

Department of Chemical and Systems Biology, Stanford University School of Medicine; Department of Biochemistry, Stanford University School of Medicine.

Traditionally used for bulk biochemical assays, Xenopus laevis egg extracts have emerged as a powerful imaging-based tool for studying cytoplasmic phenomena, such as cytokinesis, mitotic spindle formation and assembly of the nucleus. Building upon early methods that imaged fixed extracts sampled at sparse time points, recent approaches image live extracts using time-lapse microscopy, revealing more dynamical features with enhanced temporal resolution. These methods usually require sophisticated surface treatments of the imaging vessel. Read More

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Exposure to Copper Compromises the Maturational Competency of Porcine Oocytes by Impairing Mitochondrial Function.

Front Cell Dev Biol 2021 4;9:678665. Epub 2021 Jun 4.

College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.

Copper (Cu) is an essential trace element for animals, and also an important nutritional component for the normal physiology and metabolism of animal reproductive systems. An excess or lack of Cu will directly or indirectly affect animal reproductive activities. However, the effect of Cu, in particular excessive Cu, on the reproductive performance of sows has not been studied. Read More

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A CLK1-KKT2 Signaling Pathway Regulating Kinetochore Assembly in Trypanosoma brucei.

mBio 2021 Jun 15:e0068721. Epub 2021 Jun 15.

York Biomedical Research Institute, Department of Biology, University of York, Heslington, United Kingdom.

During mitosis, eukaryotic cells must duplicate and separate their chromosomes in a precise and timely manner. The apparatus responsible for this is the kinetochore, which is a large protein structure that links chromosomal DNA and spindle microtubules to facilitate chromosome alignment and segregation. The proteins that comprise the kinetochore in the protozoan parasite Trypanosoma brucei are divergent from yeast and mammals and comprise an inner kinetochore complex composed of 24 distinct proteins (KKT1 to KKT23, KKT25) that include four protein kinases, CLK1 (KKT10), CLK2 (KKT19), KKT2, and KKT3. Read More

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Semin Cell Dev Biol 2021 Jun 11. Epub 2021 Jun 11.

Chromosome Instability & Dynamics Group, i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; Cell Division Group, Experimental Biology Unit, Department of Biomedicine, Faculdade de Medicina, Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal. Electronic address:

The establishment of a metaphase plate in which all chromosomes are attached to mitotic spindle microtubules and aligned at the cell equator is required for faithful chromosome segregation in metazoans. The achievement of this configuration relies on the precise coordination between several concurrent mechanisms that start upon nuclear envelope breakdown, mediate chromosome capture at their kinetochores during mitotic spindle assembly and culminate with the congression of all chromosomes to the spindle equator. This period is called 'prometaphase'. Read More

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Echinoderm Microtubule Associated Protein Like 1 Is Indispensable for Oocyte Spindle Assembly and Meiotic Progression in Mice.

Front Cell Dev Biol 2021 28;9:687522. Epub 2021 May 28.

State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.

Completion of the first meiosis is an essential prerequisite for producing a functionally normal egg for fertilization and embryogenesis, but the precise mechanisms governing oocyte meiotic progression remains largely unclear. Here, we report that echinoderm microtubule associated protein (EMAP) like 1 (EML1), a member of the conserved EMAP family proteins, plays a crucial role in the control of oocyte meiotic progression in the mouse. Female mice carrying an ENU-induced nonsense mutation (c. Read More

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Ubiquitin Signaling in the Control of Centriole Duplication.

FEBS J 2021 Jun 11. Epub 2021 Jun 11.

School of Biology, Indian Institute of Science Education and Research, Thiruvananthapuram, Vithura, Thiruvananthapuram, 695551, Kerala, India.

Centrosome plays essential roles in maintaining genetic stability, ciliogenesis and cell polarization. The core of centrosome is made of two centrioles that duplicate precisely once during every cell cycle to generate two centrosomes that are required for bipolar spindle assembly and chromosome segregation. Abundance of centriole proteins at optimal levels and their recruitment to the centrosome are tightly regulated in time and space in order to restrict aberrant duplication of centrioles, a phenomenon that is observed in many cancers. Read More

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Mapping Proximity Associations of Core Spindle Assembly Checkpoint Proteins.

J Proteome Res 2021 Jun 4. Epub 2021 Jun 4.

Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, United States.

The spindle assembly checkpoint (SAC) is critical for sensing defective microtubule-kinetochore attachments and tension across the kinetochore and functions to arrest cells in prometaphase to allow time to repair any errors before proceeding into anaphase. Dysregulation of the SAC leads to chromosome segregation errors that have been linked to human diseases like cancer. Although much has been learned about the composition of the SAC and the factors that regulate its activity, the proximity associations of core SAC components have not been explored in a systematic manner. Read More

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High-Resolution Analysis of Centrosome Behavior During Mitosis.

Methods Mol Biol 2021 ;2329:179-194

Instituto de Investigação e Inovação em Saúde (i3S), Porto, Portugal.

Cell division requires a dynamic reorganization of cytoskeletal and nuclear components. One essential step is the separation of centrosomes, which allows the assembly of a microtubule-based mitotic spindle. This has to be spatially and temporally coordinated with other events such as adhesion complex disengagement, assembly of an actin-rich cell cortex and nuclear envelope breakdown (NEB), to ensure chromosome segregation fidelity. Read More

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January 2021

Mitotic syndicates Aurora Kinase B (AURKB) and mitotic arrest deficient 2 like 2 (MAD2L2) in cohorts of DNA damage response (DDR) and tumorigenesis.

Mutat Res 2021 Jan-Jun;787:108376. Epub 2021 Apr 24.

SA-MRC/UP Precision Prevention and Novel Drug Targets for HIV-Associated Cancers Extramural Unit, Pan African Cancer Research Institute, Faculty of Health Sciences, University of Pretoria, Hatfield, 0028, South Africa.

Aurora Kinase B (AURKB) and Mitotic Arrest Deficient 2 Like 2 (MAD2L2) are emerging anticancer therapeutic targets. AURKB and MAD2L2 are the least well studied members of their protein families, compared to AURKA and MAD2L1. Both AURKB and MAD2L2 play a critical role in mitosis, cell cycle checkpoint, DNA damage response (DDR) and normal physiological processes. Read More

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Checkpoint kinases are required for oocyte meiotic progression by the maintenance of normal spindle structure and chromosome condensation.

Exp Cell Res 2021 May 31;405(2):112657. Epub 2021 May 31.

Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Education Ministry of China, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China. Electronic address:

Checkpoint kinases (Chk) 1/2 are known for DNA damage checkpoint and cell cycle control in somatic cells. According to recent findings, the involvement of Chk1 in oocyte meiotic resumption and Chk2 is regarded as an essential regulator for progression at the post metaphase I stage (MI). In this study, AZD7762 (Chk1/2 inhibitor) and SB218078 (Chk1 inhibitor) were used to uncover the joint roles of Chk1/2 and differentiate the importance of Chk1 and Chk2 during oocyte meiotic maturation. Read More

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Ctf3/CENP-I provides a docking site for the desumoylase Ulp2 at the kinetochore.

J Cell Biol 2021 Aug 3;220(8). Epub 2021 Jun 3.

Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA.

The step-by-step process of chromosome segregation defines the stages of the cell cycle. In eukaryotes, signals controlling these steps converge upon the kinetochore, a multiprotein assembly that connects spindle microtubules to chromosomal centromeres. Kinetochores control and adapt to major chromosomal transactions, including replication of centromeric DNA, biorientation of sister centromeres on the metaphase spindle, and transit of sister chromatids into daughter cells during anaphase. Read More

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LMBD1 protein participates in cell mitosis by regulating microtubule assembly.

Biochem J 2021 Jun 2. Epub 2021 Jun 2.

National Taiwan University, Taipei, Taiwan.

LMBD1 was previously demonstrated to regulate the endocytosis of insulin receptor on cell surface and to mediate the export of cobalamin from the lysosomes to cytosol, but little is known about its function in mitosis. In this study, interactome analysis data indicate that LMBD1 is involved in cytoskeleton regulation. Both immunoprecipitation and GST pulldown assays demonstrated association of LMBD1 with tubulin. Read More

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The Organization of the Golgi Structures during Drosophila Male Meiosis Requires the Citrate Lyase ATPCL.

Int J Mol Sci 2021 May 27;22(11). Epub 2021 May 27.

Dipartimento di Biologia e Biotecnologie "Charles Darwin", Sapienza-Università di Roma, 00185 Rome, Italy.

During spermatogenesis, the Golgi apparatus serves important roles including the formation of the acrosome, which is a sperm-specific organelle essential for fertilization. We have previously demonstrated that ATP-dependent Citrate Lyase (ATPCL) is required for spindle organization, cytokinesis, and fusome assembly during male meiosis, mainly due to is activity on fatty acid biosynthesis. Here, we show that depletion of also affects the organization of acrosome and suggest a role for this enzyme in the assembly of Golgi-derived structures during Drosophila spermatogenesis. Read More

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Combination Treatment of OSI-906 with Aurora B Inhibitor Reduces Cell Viability via Cyclin B1 Degradation-Induced Mitotic Slippage.

Int J Mol Sci 2021 May 27;22(11). Epub 2021 May 27.

Department of Biochemistry & Molecular Biology, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.

Insulin-like growth factor 1 receptor (IGF1R), a receptor-type tyrosine kinase, transduces signals related to cell proliferation, survival, and differentiation. We recently reported that OSI-906, an IGF1R inhibitor, in combination with the Aurora B inhibitor ZM447439 suppresses cell proliferation. However, the mechanism underlying this suppressive effect is yet to be elucidated. Read More

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SUMO proteases SENP3 and SENP5 spatiotemporally regulate the kinase activity of Aurora A.

J Cell Sci 2021 Jun 1. Epub 2021 Jun 1.

Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China.

Precise chromosome segregation is mediated by a well-assembled mitotic spindle, which requires balance of the kinase activity of Aurora A (AurA). However, how this kinase activity is regulated remains largely unclear. Here, using in vivo and in vitro assays, we report that conjugation of SUMO2 with AurA at K258 in early mitosis promotes the kinase activity of AurA and facilitates the binding with its activator, Bora. Read More

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WDR62 is required for centriole duplication in spermatogenesis and manchette removal in spermiogenesis.

Commun Biol 2021 May 31;4(1):645. Epub 2021 May 31.

School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.

WDR62 is a scaffold protein involved in centriole duplication and spindle assembly during mitosis. Mutations in WDR62 can cause primary microcephaly and premature ovarian insufficiency. We have generated a genetrap mouse model deficient in WDR62 and characterised the developmental effects of WDR62 deficiency during meiosis in the testis. Read More

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SIK2 kinase synthetic lethality is driven by spindle assembly defects in FANCA-deficient cells.

Mol Oncol 2021 May 31. Epub 2021 May 31.

Department of Pediatrics, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.

The Fanconi anemia (FA) pathway safeguards genomic stability through cell cycle regulation and DNA damage repair. The canonical tumor suppressive role of FA proteins in the repair of DNA damage during interphase is well established, but their function in mitosis is incompletely understood. Here we performed a kinome-wide synthetic lethality screen in FANCA-/- fibroblasts, which revealed multiple mitotic kinases as necessary for survival of FANCA-deficient cells. Read More

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Vanadocene dichloride induces apoptosis in HeLa cells through depolymerization of microtubules and inhibition of Eg5.

J Biol Inorg Chem 2021 Jun 31;26(4):511-531. Epub 2021 May 31.

School of Biotechnology, National Institute of Technology Calicut, Calicut, Kerala, 673601, India.

Vanadocene dichloride (VDC), a vanadium containing metallocene dihalide exhibits promising anticancer activity. However, its mechanism of action remains elusive as several diverse targets and pathways have been proposed for its anticancer activity. In this study, we observed that VDC inhibited the proliferation of mammalian cancer cells and induced apoptotic cell death by altering the mitochondrial membrane potential and the expression of bcl2 and bax. Read More

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Aurora kinase A, a synthetic lethal target for precision cancer medicine.

Exp Mol Med 2021 May 28;53(5):835-847. Epub 2021 May 28.

Cancer Centre, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.

Recent advances in high-throughput sequencing technologies and data science have facilitated the development of precision medicine to treat cancer patients. Synthetic lethality is one of the core methodologies employed in precision cancer medicine. Synthetic lethality describes the phenomenon of the interplay between two genes in which deficiency of a single gene does not abolish cell viability but combined deficiency of two genes leads to cell death. Read More

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Selective targeting of non-centrosomal AURKA functions through use of a targeted protein degradation tool.

Commun Biol 2021 May 28;4(1):640. Epub 2021 May 28.

Department of Pharmacology, University of Cambridge, Cambridge, UK.

Targeted protein degradation tools are becoming a new therapeutic modality, allowing small molecule ligands to be reformulated as heterobifunctional molecules (PROteolysis Targeting Chimeras, PROTACs) that recruit ubiquitin ligases to targets of interest, leading to ubiquitination and destruction of the targets. Several PROTACs against targets of clinical interest have been described, but detailed descriptions of the cell biology modulated by PROTACs are missing from the literature. Here we describe the functional characterization of a PROTAC derived from AURKA inhibitor MLN8237 (alisertib). Read More

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Energy restriction causes metaphase delay and chromosome mis-segregation in cancer cells.

Cell Cycle 2021 May 28:1-14. Epub 2021 May 28.

The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

ATP metabolism during mitosis needs to be coordinated with numerous energy-demanding activities, especially in cancer cells whose metabolic pathways are reprogramed to sustain rapid proliferation in a nutrient-deficient environment. Although strategies targeting the energy metabolic pathways have shown therapeutic efficacy in preclinical cancer models, how normal cells and cancer cells differentially respond to energy shortage is unclear. In this study, using time-lapse microscopy, we found that cancer cells displayed unique mitotic phenotypes in a dose-dependent manner upon decreasing ATP (i. Read More

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Aurora B kinase: a potential drug target for cancer therapy.

J Cancer Res Clin Oncol 2021 May 28. Epub 2021 May 28.

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India.

Background: Ensuring genetic integrity is essential during the cell cycle to avoid aneuploidy, one of the underlying causes of malignancies. Aurora kinases are serine/threonine kinase that play a vital role in maintaining the genomic integrity of the cells. There are three forms of aurora kinases in the mammalian cells, which are highly conserved and act together with several other proteins to control chromosome alignment and its equal distribution to daughter cells in mitosis and meiosis. Read More

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The multifunctional spindle midzone in vertebrate cells at a glance.

J Cell Sci 2021 May 27;134(10). Epub 2021 May 27.

Department of Biology, Morrill Science Center, University of Massachusetts, 611 N. Pleasant Street, Amherst 01003, USA.

During anaphase, a microtubule-containing structure called the midzone forms between the segregating chromosomes. The midzone is composed of an antiparallel array of microtubules and numerous microtubule-associated proteins that contribute to midzone formation and function. In many cells, the midzone is an important source of signals that specify the location of contractile ring assembly and constriction. Read More

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Confinement size determines the architecture of Ran-induced microtubule networks.

Soft Matter 2021 May 27. Epub 2021 May 27.

Department of Molecular Biology, Princeton University, Princeton, NJ, USA.

The organization of microtubules (MTs) is critical for cells during interphase and mitosis. During mitotic spindle assembly, MTs are made and organized around chromosomes in a process regulated by RanGTP. The role of RanGTP has been explored in Xenopus egg extracts, which are not limited by a cell membrane. Read More

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Spastin interacts with CRMP5 to promote spindle organization in mouse oocytes by severing microtubules.

Zygote 2021 May 26:1-12. Epub 2021 May 26.

Department of Gynaecology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang310014, China.

Microtubule-severing protein (MTSP) is critical for the survival of both mitotic and postmitotic cells. However, the study of MTSP during meiosis of mammalian oocytes has not been reported. We found that spastin, a member of the MTSP family, was highly expressed in oocytes and aggregated in spindle microtubules. Read More

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