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PMID: 11756469 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

CENP-A is phosphorylated by Aurora B kinase and plays an unexpected role in completion of cytokinesis.

The Journal of cell biology ·Vol. 155 ·No. 7 ·2001-12-24 ·Pages 1147-57

Zeitlin SG, Shelby RD, Sullivan KF

Abstract

Aurora B is a mitotic protein kinase that phosphorylates histone H3, behaves as a chromosomal passenger protein, and functions in cytokinesis. We investigated a role for Aurora B with respect to human centromere protein A (CENP-A), a centromeric histone H3 homologue. Aurora B concentrates at centromeres in early G2, associates with histone H3 and centromeres at the times when histone H3 and CENP-A are phosphorylated, and phosphorylates histone H3 and CENP-A in vitro at a similar target serine residue. Dominant negative phosphorylation site mutants of CENP-A result in a delay at the terminal stage of cytokinesis (cell separation). The only molecular defects detected in analysis of 22 chromosomal, spindle, and regulatory proteins were disruptions in localization of inner centromere protein (INCENP), Aurora B, and a putative partner phosphatase, PP1gamma1. Our data support a model where CENP-A phosphorylation is involved in regulating Aurora B, INCENP, and PP1gamma1 targeting within the cell. These experiments identify an unexpected role for the kinetochore in regulation of cytokinesis.

MeSH Terms
Animals Aurora Kinase B Aurora Kinases Autoantigens Blotting, Western Caenorhabditis elegans/metabolism Cell Line Centromere/physiology Centromere Protein A Chromosomal Proteins, Non-Histone/analysis,genetics,metabolism Cytokines/genetics Electrophoresis, Polyacrylamide Gel Fluorescent Antibody Technique Histones/metabolism Humans Mitosis Mutagenesis, Site-Directed Phosphoprotein Phosphatases/metabolism Phosphorylation Protein Serine-Threonine Kinases/metabolism Recombinant Proteins/metabolism Saccharomyces cerevisiae/metabolism Transfection
Chemicals
Autoantigens CENPA protein, human Centromere Protein A Chromosomal Proteins, Non-Histone Cytokines Histones Recombinant Proteins AURKB protein, human Aurora Kinase B Aurora Kinases Protein Serine-Threonine Kinases Phosphoprotein Phosphatases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Zeitlin S G
Department of Cell Biology, Scripps Research Institute, La Jolla, CA 92037, USA.
Shelby R D
Sullivan K F
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200108125
Published
2001-12-24
Epub
2001-00-24
Pages
1147-57
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2199334
Subset
IM
Grants
NIGMS NIH HHS · R01 GM039068 · United States
NIGMS NIH HHS · GM39068 · United States
External Links
PubMed source DOI: 10.1083/jcb.200108125 PMC Full Text View journal details
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