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rdf:type |
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lifeskim:mentions |
umls-concept:C0037083,
umls-concept:C0205314,
umls-concept:C0309311,
umls-concept:C0542341,
umls-concept:C0679622,
umls-concept:C1337107,
umls-concept:C1416958,
umls-concept:C1417672,
umls-concept:C1622917,
umls-concept:C1706057,
umls-concept:C1710082,
umls-concept:C2362652
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pubmed:issue |
19
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pubmed:dateCreated |
2004-5-4
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pubmed:abstractText |
Chromosome segregation in mitosis is orchestrated by protein kinase signaling cascades. A biochemical cascade named spindle checkpoint ensures the spatial and temporal order of chromosome segregation during mitosis. Here we report that spindle checkpoint protein MAD1 interacts with NEK2A, a human orthologue of the Aspergillus nidulans NIMA kinase. MAD1 interacts with NEK2A in vitro and in vivo via a leucine zipper-containing domain located at the C terminus of MAD1. Like MAD1, NEK2A is localized to HeLa cell kinetochore of mitotic cells. Elimination of NEK2A by small interfering RNA does not arrest cells in mitosis but causes aberrant premature chromosome segregation. NEK2A is required for MAD2 but not MAD1, BUB1, and HEC1 to associate with kinetochores. These NEK2A-eliminated or -suppressed cells display a chromosome bridge phenotype with sister chromatid inter-connected. Moreover, loss of NEK2A impairs mitotic checkpoint signaling in response to spindle damage by nocodazole, which affected mitotic escape and led to generation of cells with multiple nuclei. Our data demonstrate that NEK2A is a kinetochore-associated protein kinase essential for faithful chromosome segregation. We hypothesize that NEK2A links MAD2 molecular dynamics to spindle checkpoint signaling.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/MAD1L1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/NEK2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nocodazole,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
7
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
20049-57
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:14978040-Amino Acid Motifs,
pubmed-meshheading:14978040-Aspergillus nidulans,
pubmed-meshheading:14978040-Blotting, Western,
pubmed-meshheading:14978040-Cell Cycle Proteins,
pubmed-meshheading:14978040-DNA, Complementary,
pubmed-meshheading:14978040-Glutathione Transferase,
pubmed-meshheading:14978040-HeLa Cells,
pubmed-meshheading:14978040-Humans,
pubmed-meshheading:14978040-Kinetochores,
pubmed-meshheading:14978040-Microscopy, Fluorescence,
pubmed-meshheading:14978040-Mitosis,
pubmed-meshheading:14978040-Mitotic Spindle Apparatus,
pubmed-meshheading:14978040-Nocodazole,
pubmed-meshheading:14978040-Nuclear Proteins,
pubmed-meshheading:14978040-Phenotype,
pubmed-meshheading:14978040-Phosphoproteins,
pubmed-meshheading:14978040-Precipitin Tests,
pubmed-meshheading:14978040-Protein Binding,
pubmed-meshheading:14978040-Protein Structure, Tertiary,
pubmed-meshheading:14978040-Protein-Serine-Threonine Kinases,
pubmed-meshheading:14978040-RNA, Small Interfering,
pubmed-meshheading:14978040-Recombinant Proteins,
pubmed-meshheading:14978040-Repressor Proteins,
pubmed-meshheading:14978040-Signal Transduction,
pubmed-meshheading:14978040-Sister Chromatid Exchange,
pubmed-meshheading:14978040-Transfection,
pubmed-meshheading:14978040-Two-Hybrid System Techniques
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pubmed:year |
2004
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pubmed:articleTitle |
NEK2A interacts with MAD1 and possibly functions as a novel integrator of the spindle checkpoint signaling.
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pubmed:affiliation |
School of Life Sciences, University of Science & Technology of China, Hefei 230027, China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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