CENP-E forms a link between attachment of spindle microtubules to kinetochores and the mitotic checkpoint.
Here we show that suppression of synthesis of the microtubule motor 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. Despite apparently normal microtubule numbers and the continued presence at kinetochores of other microtubule motors, spindle poles fragment in the absence of CENP-E, which implicates this protein in delivery of components from kinetochores to poles. CENP-E represents a link between attachment of spindle microtubules and the mitotic checkpoint signalling cascade, as depletion of this motor leads to profound checkpoint activation, whereas immunoprecipitation reveals a nearly stoichiometric association of CENP-E with the checkpoint kinase BubR1 during mitosis.
Department of Physiology, University of Wisconsin, Madison, Wisconsin 53706, USA.
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X
Yao
A
A
Abrieu
Y
Y
Zheng
K F
KF
Sullivan
D W
DW
Cleveland
D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D002877:Chromosomes, Human / Q000235:genetics / Q000378:metabolism*; D019926:Cyclin B / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis; D008940:Mitotic Index; D008954:Models, Biological; D016376:Oligonucleotides, Antisense / Q000235:genetics; D011233:Precipitin Tests; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000737:chemistry / Q000378:metabolism*; D014162:Transfection
D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D019926:Cyclin B; D016376:Oligonucleotides, Antisense; C068688:centromere protein E; D011494:Protein Kinases; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases