Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.4.4 (kinesin)
5,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During cytokinesis, the organization of the spindle midzone and chromosome segregation is controlled by the central spindle, a microtubule cytoskeleton containing kinesin motors and non-motor microtubule-associated proteins. The anaphase spindle elongation 1/protein regulator of cytokinesis 1/microtubule associated protein 65 (Ase1/PRC1/MAP65) family of microtubule-bundling proteins are key regulators of central spindle assembly, mediating microtubule crosslinking and spindle elongation in the midzone. Ase1/PRC1/MAP65 serves as a complex regulatory platform for the recruitment of other midzone proteins at the spindle midzone. Herein, we summarize recent advances in understanding of the structural domains and molecular kinetics of the Ase1/PRC1/MAP65 family. We summarize the regulatory network involved in post-translational modifications of Ase1/PRC1 by cyclin-dependent kinase 1 (Cdk1), cell division cycle 14 (Cdc14) and Polo-like kinase 1 (Plk1) and also highlight multiple functions of Ase1/PRC1 in central spindle organization, spindle elongation and cytokinesis during cell division.
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PMID:Mechanisms of the Ase1/PRC1/MAP65 family in central spindle assembly. 3134 16

The aim of the present study was to identify genes associated with and the underlying mechanisms in nasopharyngeal carcinoma (NPC) using microarray data. GSE12452 and GSE34573 gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database. GEO2R was utilized to obtain differentially expressed genes (DEGs). In addition, the Database for Annotation, Visualization and Integrated Discovery was used to perform pathway enrichment analyses for DEGs using the Gene Ontology (GO) annotation along with the Kyoto Encyclopedia of Genes and Genomes (KEGG). Furthermore, Cytoscape was used to perform module analysis of the protein-protein interaction (PPI) network and pathways of the hub genes were studied. A total of 298 genes were ascertained as DEGs in the two datasets. To functionally categorize these DEGs, we obtained 82 supplemented GO terms along with 7 KEGG pathways. Subsequently, a PPI network consisting of 10 hub genes with high degrees of interaction was constructed. These hub genes included cyclin-dependent kinase (CDK) 1, structural maintenance of chromosomes (SMC) 4, kinetochore-associated (KNTC) 1, kinesin family member (KIF) 23, aurora kinase A (AURKA), ATAD (ATPase family AAA domain containing) 2, NDC80 kinetochore complex component, enhancer of zeste 2 polycomb repressive complex 2 subunit, BUB1 mitotic checkpoint serine/threonine kinase and protein regulator of cytokinesis 1. CDK1, SMC4, KNTC1, KIF23, AURKA and ATAD2 presented with high areas under the curve in receiver operator curves, suggesting that these genes may be diagnostic markers for nasopharyngeal carcinoma. In conclusion, it was proposed that CDK1, SMC4, KNTC1, KIF23, AURKA and ATAD2 may be involved in the tumorigenesis of NPC. Furthermore, they may be utilized as molecular biomarkers in early diagnosis of NPC.
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PMID:Bioinformatics analysis identifies hub genes and pathways in nasopharyngeal carcinoma. 3151 77

Antiparallel microtubule bundles are essential structural elements of many cytoskeletal structures, for instance, the mitotic spindle. Sliding of microtubules relative to each other can lead to an overall elongation of the bundle. However, such sliding must be accompanied by microtubule growth, to maintain the overlap, which is a landmark of anaphase. Diffusive crosslinkers of the Ase1/PRC1/MAP65 family are able to form stable overlaps in combination with kinesin-14 motors. This process is thought to arise through a balance of forces between motors and crosslinkers, the latter effectively producing an entropic pressure. We provide a continuous theory to explain the formation of stable overlaps, in which steric effects caused by the finite number of binding sites available on the microtubule lattice play a leading role. We confirmed the validity of this approach using discrete stochastic simulations performed with the Open Source simulation engine Cytosim. From the densities of motors and crosslinkers, their diffusion rates, and the velocities of motors, the theory predicts the sliding speed of microtubules and explains the force production and breaking effect of crosslinkers and motors containing diffusible microtubule-binding domains. Finally, we discuss a mechanism by which sliding and microtubule growth can be coordinated without the need for fine-tuning the parameters of the system, in line with the known robustness of mitosis.
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PMID:Theory of antiparallel microtubule overlap stabilization by motors and diffusible crosslinkers. 3290 70

Aurora kinases create phosphorylation gradients within the spindle during prometaphase and anaphase, thereby locally regulating factors that promote spindle organization, chromosome condensation and movement, and cytokinesis. We show that one such factor is the kinesin KIF4A, which is present along the chromosome axes throughout mitosis and the central spindle in anaphase. These two pools of KIF4A depend on condensin I and PRC1, respectively. Previous work has shown KIF4A is activated by Aurora B at the anaphase central spindle. However, whether or not chromosome-associated KIF4A bound to condensin I is regulated by Aurora kinases remain unclear. To determine the roles of the two different pools of KIF4A, we generated specific point mutants that are unable to interact with either condensin I or PRC1 or are deficient for Aurora kinase regulation. By analyzing these mutants, we show that Aurora A phosphorylates the condensin I-dependent pool of KIF4A and thus actively promotes chromosome congression from the spindle poles to the metaphase plate.
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PMID:Aurora A promotes chromosome congression by activating the condensin-dependent pool of KIF4A. 3188 Oct 80


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