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PMID:17600710

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Citation

Vergnolle, MA and Taylor, SS (2007) Cenp-F links kinetochores to Ndel1/Nde1/Lis1/dynein microtubule motor complexes. Curr. Biol. 17:1173-9

Abstract

Cenp-F is a nuclear matrix component that localizes to kinetochores during mitosis and is then rapidly degraded after mitosis [1]. Unusually, both the localization and degradation of Cenp-F require it to be farnesylated [2]. Five studies recently demonstrated that Cenp-F is required for kinetochore-microtubule interactions and spindle checkpoint function [3-7]; however, the underlying molecular mechanisms have yet to be defined. Here, we show that Cenp-F interacts with Ndel1 and Nde1, two human NudE-related proteins implicated in regulating Lis1/Dynein motor complexes (reviewed in [8]). We show that Ndel1, Nde1, and Lis1 localize to kinetochores in a Cenp-F-dependent manner. In addition, Nde1, but not Ndel1, is required for kinetochore localization of Dynein. Accordingly, suppression of Nde1 inhibits metaphase chromosome alignment and activates the spindle checkpoint. By contrast, inhibition of Ndel1 results in malorientations that are not detected by the spindle checkpoint; Ndel1-deficient cells consequently enter anaphase in a timely manner but lagging chromosomes then manifest. A major function of Cenp-F, therefore, is to link the Ndel1/Nde1/Lis1/Dynein pathway to kinetochores. Furthermore, our data demonstrate that Ndel1 and Nde1 play distinct roles to ensure chromosome alignment and segregation.

Links

PubMed Online version:10.1016/j.cub.2007.05.077

Keywords

1-Alkyl-2-acetylglycerophosphocholine Esterase/metabolism; Carrier Proteins/metabolism; Chromosomal Proteins, Non-Histone/metabolism; Chromosome Segregation/physiology; Dyneins/metabolism; HeLa Cells; Humans; Kinetochores/metabolism; Microfilament Proteins/metabolism; Microtubule-Associated Proteins/metabolism; Microtubules/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:CENPF

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9GZM8

F

Seeded From UniProt

complete

HUMAN:CENPF

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9NXR1

F

Seeded From UniProt

complete

HUMAN:CENPF

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9GZM8

F

Seeded From UniProt

complete

HUMAN:NDEL1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P49454

F

Seeded From UniProt

complete

HUMAN:NDEL1

located_in

GO:0000776: kinetochore

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:NDEL1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P49454

F

Seeded From UniProt

complete

HUMAN:NDE1

located_in

GO:0000776: kinetochore

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:NDE1

involved_in

GO:0051303: establishment of chromosome localization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:NDE1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P49454

F

Seeded From UniProt

complete

HUMAN:NDEL1

involved_in

GO:0007059: chromosome segregation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:NDEL1

part_of

GO:0000776: kinetochore

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CENPF

involved_in

GO:0015031: protein transport

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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