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PMID: 11950927 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The Schizosaccharomyces pombe aurora-related kinase Ark1 interacts with the inner centromere protein Pic1 and mediates chromosome segregation and cytokinesis.

Molecular biology of the cell ·Vol. 13 ·No. 4 ·2002-04-00 ·Pages 1132-43

Leverson JD, Huang HK, Forsburg SL, Hunter T

Abstract

The chromosomal passenger proteins aurora-B, survivin, and inner centromere protein (INCENP) have been implicated in coordinating chromosome segregation with cell division. This work describes the interplay between aurora, survivin, and INCENP orthologs in the fission yeast Schizosaccharomyces pombe and defines their roles in regulating chromosome segregation and cytokinesis. We describe the cloning and characterization of the aurora-related kinase gene ark1(+), demonstrating that it is an essential gene required for sister chromatid segregation. Cells lacking Ark1p exhibit the cut phenotype, DNA fragmentation, and other defects in chromosome segregation. Overexpression of a kinase-defective version of Ark1, Ark1-K147R, inhibits cytokinesis, with cells exhibiting an elongated, multiseptate phenotype. Ark1p interacts physically and/or genetically with the survivin and INCENP orthologs Bir1p and Pic1p. We identified Pic1p in a two-hybrid screen for Ark1-K147R interacting partners and went on to map domains in both proteins that mediate their binding. Pic1p residues 925-972 are necessary and sufficient for Ark1p binding, which occurs through the kinase domain. As with Ark1-K147R, overexpression of Ark1p-binding fragments of Pic1p leads to multiseptate phenotypes. We also provide evidence that the dominant-negative effect of Ark1-K147R requires Pic1p binding, indicating that the formation of Ark1p-Pic1p complexes is required for the execution of cytokinesis.

MeSH Terms
Aurora Kinases Cell Division Centromere/metabolism Chromosome Segregation Chromosomes/metabolism Cloning, Molecular Genes, Dominant Glutathione Transferase/metabolism Microscopy, Fluorescence Models, Genetic Mutagenesis, Site-Directed Mutation Phosphorylation Potassium Channels/metabolism Protein Binding Protein Serine-Threonine Kinases/metabolism,physiology Protein Structure, Tertiary Recombinant Fusion Proteins/metabolism SUMO-1 Protein/metabolism Schizosaccharomyces/enzymology Schizosaccharomyces pombe Proteins Time Factors Two-Hybrid System Techniques
Chemicals
Potassium Channels Recombinant Fusion Proteins SUMO-1 Protein Schizosaccharomyces pombe Proteins Glutathione Transferase Aurora Kinases Protein Serine-Threonine Kinases ark1 protein, S pombe
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Leverson Joel D
Molecular and Cell Biology Laboratory, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037.
Huang Han-kuei
Forsburg Susan L
Hunter Tony
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.01-07-0330
Published
2002-04-00
Pages
1132-43
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC102257
Subset
IM
Grants
NCI NIH HHS · P30 CA014195 · United States
NCI NIH HHS · R01 CA080100 · United States
NCI NIH HHS · CA-14195 · United States
NCI NIH HHS · CA-80100 · United States
External Links
PubMed source DOI: 10.1091/mbc.01-07-0330 PMC Full Text View journal details
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