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The microtubule-dependent motor centromere-associated protein E (CENP-E) is an integral component of kinetochore corona fibers that link centromeres to spindle microtubules.

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TLDR
Evidence is presented that strongly supports a model in which CENP-E functions in congression to tether kinetochores to the disassembling microtubule plus ends.
Abstract
Centromere-associated protein E (CENP-E) is a kinesin-related microtubule motor protein that is essential for chromosome congression during mitosis. Using immunoelectron microscopy, CENP-E is shown to be an integral component of the kinetochore corona fibers that tether centromeres to the spindle. Immediately upon nuclear envelope fragmentation, an associated plus end motor trafficks cytoplasmic CENP-E toward chromosomes along astral microtubules that enter the nuclear volume. Before or concurrently with initial lateral attachment of spindle microtubules, CENP-E targets to the outermost region of the developing kinetochores. After stable attachment, throughout chromosome congression, at metaphase, and throughout anaphase A, CENP-E is a constituent of the corona fibers, extending at least 50 nm away from the kinetochore outer plate and intertwining with spindle microtubules. In congressing chromosomes, CENP-E is preferentially associated with (or accessible at) the stretched, leading kinetochore known to provide the primary power for chromosome movement. Taken together, this evidence strongly supports a model in which CENP-E functions in congression to tether kinetochores to the disassembling microtubule plus ends.

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Journal ArticleDOI

Targeted anti-mitotic therapies: can we improve on tubulin agents?

TL;DR: The advent of molecularly targeted drug discovery has facilitated the identification of a new generation of anti-mitotic therapies that target proteins with specific functions in mitosis, and these potential therapies serve as unique tools to dissect the molecular mechanisms of the mitotic-checkpoint response.
Journal ArticleDOI

A Molecular View of Kinetochore Assembly and Function.

TL;DR: A broad summary of progress in the elucidation of the composition of the kinetochore and the identification of various physical and functional modules within its substructure has led to a much deeper molecular understanding of kinetchore organization and the origins of its functional output.
Journal ArticleDOI

Chromosomes Can Congress to the Metaphase Plate Before Biorientation

TL;DR: In mammalian cells, it is found that chromosomes can congress before becoming bioriented, and this congression mechanism depended on the kinetochore-associated, plus end–directed microtubule motor CENP-E (kinesin-7).
Journal ArticleDOI

The dynamic kinetochore-microtubule interface.

TL;DR: The kinetochore is a control module that both powers and regulates chromosome segregation in mitosis and meiosis, and recent work has revealed that many kinetchore components are highly dynamic and that some cycle between Kinetochores and spindle poles along microtubules.
Journal ArticleDOI

CENP-E forms a link between attachment of spindle microtubules to kinetochores and the mitotic checkpoint

TL;DR: In this article, it was shown that the absence of CENP-E (centromere-associated protein E), a component of the kinetochore corona fibres of mammalian centromeres, yields chromosomes that are chronically mono-orientated, with spindles that are flattened along the plane of the substrate.
References
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Book

Antibodies: A Laboratory Manual

Ed Harlow, +1 more
TL;DR: A second edition of Antibodies: A Laboratory Manual is being published in September 2013, Revised, extended and updated by Edward Greenfield of the Dana-Farber Cancer Center, the material has been recast with extensive new information and new chapters have been added.
Journal ArticleDOI

Self-organization of microtubules into bipolar spindles around artificial chromosomes in Xenopus egg extracts

TL;DR: Functional nuclei and mitotic spindles are shown to assemble around DNA-coated beads incubated in Xenopus egg extracts, indicating that bipolarity is an intrinsic property of microtubules assembling around chromatin in a mitotic cytoplasm.
Journal ArticleDOI

Rat monoclonal antitubulin antibodies derived by using a new nonsecreting rat cell line.

TL;DR: The antitubulin antibodies in the serum of rats bearing two of the hybrid myeloma tumors gave titers of up to 1:10(6) from which large amounts of monoclonal antibodies could be easily purified and gave clear immunofluorescent staining of yeast mitotic spindles as well as the interphase microtubule network of tissue culture cells.
Journal ArticleDOI

Association of Spindle Assembly Checkpoint Component XMAD2 with Unattached Kinetochores

TL;DR: This study furthers understanding of the mechanism of cell cycle checkpoints in metazoa and provides a marker for studying the role of the spindle assembly checkpoint in the genetic instability of tumors.
Journal ArticleDOI

The checkpoint delaying anaphase in response to chromosome monoorientation is mediated by an inhibitory signal produced by unattached kinetochores.

TL;DR: The data reveal that molecules in or near the unattached kinetochore of a monooriented PtK1 chromosome inhibit the metaphase-anaphase transition.
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