Binding partner switching on microtubules and aurora-B in the mitosis to cytokinesis transition.
The cytoskeleton globally reorganizes between mitosis (M phase) and cytokinesis (C phase), which presumably requires extensive regulatory changes. To reveal these changes, we undertook a comparative proteomics analysis of cells tightly drug-synchronized in each phase. We identified 25 proteins that bind selectively to microtubules in C phase and identified several novel binding partners including nucleolar and spindle-associated protein. C phase-selective microtubule binding of many of these proteins depended on activity of Aurora kinases as assayed by treatment with the drug VX680. Aurora-B binding partners switched dramatically between M phase to C phase, and we identified several novel C phase-selective Aurora-B binding partners including PRC1, KIF4, and anaphase-promoting complex/cyclosome. Our approach can be extended to other cellular compartments and cell states, and our data provide the first broad biochemical framework for understanding C phase. Concretely, we report a central role for Aurora-B in regulating the C phase cytoskeleton.
Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nurhan
N
Ozlü
Flavio
F
Monigatti
Bernhard Y
BY
Renard
Christine M
CM
Field
Hanno
H
Steen
Timothy J
TJ
Mitchison
Judith J
JJ
Steen
D064107:Aurora Kinase B; D064127:Aurora Kinases; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D048749:Cytokinesis / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D007399:Interphase / Q000187:drug effects; D007553:Isotope Labeling; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D008938:Mitosis / Q000187:drug effects; D008954:Models, Biological; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*
D018797:Cell Cycle Proteins; C003724:3-tritylthio-L-alanine; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D003545:Cysteine