Molecular Biology of the Cell click for CBE Life Science Education Page

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

MBC in Press, published online ahead of print August 20, 2008
Mol. Biol. Cell 10.1091/mbc.E08-05-0460

A more recent version of this article appeared on November 1, 2008
This Article
Right arrow Full Text (PDF)
Right arrow Supplemental Materials
Right arrow All Versions of this Article:
E08-05-0460v1
19/11/4852    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wang, W.
Right arrow Articles by Brautigan, David. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wang, W.
Right arrow Articles by Brautigan, David. L.

Submitted on May 6, 2008
Accepted on August 8, 2008

Phosphatase Inhibitor-2 Balances Protein Phosphatase 1 and Aurora B Kinase for Chromosome Segregation and Cytokinesis in Human Retinal Epithelial Cells

Weiping Wang,*{dagger} P. Todd Stukenberg,{ddagger} and David. L. Brautigan*{dagger}

*Center for Cell Signaling, Departments of {dagger}Microbiology and {ddagger}Biochemistry & Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA, 22908

Monitoring Editor: Yixian Zheng

Mitosis in S. cerevisiae depends on IPL1 kinase, which genetically interacts with GLC8. The metazoan homologue of GLC8 is inhibitor-2 (I-2), but its function is not understood. We found endogenous and ectopic I-2 localized to the spindle, midzone and midbody of mitotic human epithelial ARPE-19 cells. Knockdown of I-2 by RNAi produced multinucleated cells, with supernumerary centrosomes, multipolar spindles and lagging chromosomes during anaphase. These defects did not involve changes in levels of PP1C, and the multinuclear phenotype was rescued by overexpression of I-2. Multiple nuclei and supernumerary centrosomes required progression through the cell cycle and I-2 knockdown cells failed cytokinesis, as observed by time-lapse microscopy. Inhibition of Aurora B by hesperadin produced multinucleated cells and reduced H3S10 phosphorylation. I-2 knockdown enhanced this latter effect. Partial knockdown of PP1C alpha prevented multiple nuclei caused by either knockdown of I-2 or treatment with hesperadin. Expression of EGFP-I-2 or HA-I-2 made cells resistant to hesperadin. We propose that I-2 acts to enhance Aurora B by inhibiting specific PP1 holoenzymes that dephosphorylate Aurora B substrates necessary for chromosome segregation and cytokinesis. Conserved together throughout eukaryotic evolution, I-2, PP1 and Aurora B function interdependently during mitosis.

Address correspondence to: David. L. Brautigan (db8g{at}virginia.edu)






Home Help [Feedback] [For Subscribers] [Archive] [Search] --
Copyright © 2008 by The American Society for Cell Biology. Terms of copyright protection, warranties, and disclaimers.