Aurora B kinase activity–dependent and –independent functions of the chromosomal passenger complex in regulating sister chromatid cohesion

Aurora B kinase activity is required for successful cell division. In this paper, we show that Aurora B is phosphorylated at serine 331 (Ser331) during mitosis and that phosphorylated Aurora B localizes to kinetochores in prometaphase cells. Chk1 kinase is essential for Ser331 phosphorylation during unperturbed prometaphase or during spindle disruption by taxol but not nocodazole. Phosphorylation at Ser331 is required for optimal phosphorylation of INCENP at TSS residues, for Survivin association with the chromosomal passenger complex, and for complete Aurora B activation, but it is dispensable for Aurora B localization to centromeres, for autophosphorylation at threonine 232, and for association with INCENP. Overexpression of Aurora BS331A, in which Ser331 is mutated to alanine, results in spontaneous chromosome missegregation, cell multinucleation, unstable binding of BubR1 to kinetochores, and impaired mitotic delay in the presence of taxol. We propose that Chk1 phosphorylates Aurora B at Ser331 to fully induce Aurora B kinase activity. These results indicate that phosphorylation at Ser331 is an essential mechanism for Aurora B activation.

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Functional interplay between Aurora B kinase and Ssu72 phosphatase regulates sister chromatid cohesion

Nature Communications ◽

10.1038/ncomms3631 ◽

2013 ◽

Vol 4 (1) ◽

Cited By ~ 10

Author(s):

Hyun-Soo Kim ◽

Se-Hyuk Kim ◽

Hye-Young Park ◽

Janet Lee ◽

Jong Hyuk Yoon ◽

...

Keyword(s):

Sister Chromatid ◽

Sister Chromatid Cohesion ◽

Aurora B ◽

Aurora B Kinase ◽

Chromatid Cohesion

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Disassembly of actin and keratin networks by Aurora B kinase at the midplane of cleaving Xenopus laevis eggs

10.1101/513200 ◽

2019 ◽

Author(s):

Christine M. Field ◽

James F. Pelletier ◽

Timothy J. Mitchison

Keyword(s):

Xenopus Laevis ◽

Kinase Activity ◽

Flow Patterns ◽

Aurora B ◽

Aurora B Kinase ◽

Chromosomal Passenger Complex ◽

Chromosomal Passenger ◽

Dividing Cells ◽

Local Softening

AbstractWe investigated how bulk cytoplasm prepares for cytokinesis in Xenopus laevis eggs, which are large, rapidly dividing cells. The egg midplane is demarcated by Chromosomal Passenger Complex (CPC) localized on microtubule bundles between asters. Using an extract system and intact eggs we found that local kinase activity of the AURKB subunit of the CPC caused disassembly of F-actin and keratin between asters, and local softening of the cytoplasm as assayed by flow patterns. Beads coated with active CPC mimicked aster boundaries and caused AURKB-dependent disassembly of F-actin and keratin that propagated ~40 μm without microtubules, and much farther with microtubules present, due to CPC auto-activation. We propose that active CPC at aster boundaries locally reduces cytoplasmic stiffness by disassembling actin and keratin networks. This may help sister centrosomes move apart after mitosis, prepare a soft path for furrow ingression and/or release G-actin to build the furrow cortex.

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TOP-2 is differentially required for the proper maintenance of cohesin on meiotic chromosomes in C. elegans spermatogenesis and oogenesis

10.1101/2021.12.26.474225 ◽

2021 ◽

Author(s):

Aimee Jaramillo-Lambert ◽

Christine Kiely Rourke

Keyword(s):

Sister Chromatid ◽

Topoisomerase Ii ◽

Meiotic Chromosome ◽

Sister Chromatid Cohesion ◽

Chromosome Length ◽

Aurora B ◽

Loss Of Function ◽

Late Prophase ◽

Prophase I ◽

Chromatid Cohesion

During meiotic prophase I, accurate segregation of homologous chromosomes requires the establishment of a chromosomes with a meiosis-specific architecture. Sister chromatid cohesins and the enzyme Topoisomerase II are important components of meiotic chromosome axes, but the relationship of these proteins in the context of meiotic chromosome segregation is poorly defined. Here, we analyzed the role of Topoisomerase II (TOP-2) in the timely release of sister chromatid cohesins during spermatogenesis and oogenesis of Caenorhabditis elegans. We show that there is a different requirement for TOP-2 in meiosis of spermatogenesis and oogenesis. The loss-of-function mutation top-2(it7) results in premature REC-8 removal in spermatogenesis, but not oogenesis. This is due to a failure to maintain the HORMA-domain proteins HTP-1 and HTP-2 (HTP-1/2) on chromosome axes at diakinesis and mislocalization of the downstream components that control sister chromatid cohesion release including Aurora B kinase. In oogenesis, top-2(it7) causes a delay in the localization of Aurora B to oocyte chromosomes but can be rescued through premature activation of the maturation promoting factor via knock-down of the inhibitor kinase WEE-1.3. The delay in Aurora B localization is associated with an increase in the length of diakinesis chromosomes and wee-1.3 RNAi mediated rescue of Auorora B localization in top-2(it7) is associated with a decrease in chromosome length. Our results imply that the sex-specific effects of Topoisomerase II on sister chromatid cohesion release are due to differences in the temporal regulation of meiosis and chromosome structure in late prophase I in spermatogenesis and oogenesis.

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Use of DT40 conditional-knockout cell lines to study chromosomal passenger protein function

Biochemical Society Transactions ◽

10.1042/bst0381655 ◽

2010 ◽

Vol 38 (6) ◽

pp. 1655-1659 ◽

Cited By ~ 1

Author(s):

Xavier Fant ◽

Kumiko Samejima ◽

Ana Carvalho ◽

Hiromi Ogawa ◽

Zhenjie Xu ◽

...

Keyword(s):

Cell Lines ◽

Protein Function ◽

Kinase Activity ◽

Current Knowledge ◽

Conditional Knockout ◽

Aurora B ◽

Aurora B Kinase ◽

Chromosomal Passenger ◽

Passenger Protein

The CPC [chromosomal passenger complex; INCENP (inner centromere protein), Aurora B kinase, survivin and borealin] is implicated in many mitotic processes. In the present paper we describe how we generated DT40 conditional-knockout cell lines for incenp1 and survivin1 to better understand the role of these CPC subunits in the control of Aurora B kinase activity. These lines enabled us to reassess current knowledge of survivin function and to show that INCENP acts as a rheostat for Aurora B activity.

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INCENP and Aurora B Promote Meiotic Sister Chromatid Cohesion through Localization of the Shugoshin MEI-S332 in Drosophila

Developmental Cell ◽

10.1016/j.devcel.2006.04.021 ◽

2006 ◽

Vol 11 (1) ◽

pp. 57-68 ◽

Cited By ~ 81

Author(s):

Tamar D. Resnick ◽

David L. Satinover ◽

Fiona MacIsaac ◽

P. Todd Stukenberg ◽

William C. Earnshaw ◽

...

Keyword(s):

Sister Chromatid ◽

Sister Chromatid Cohesion ◽

Aurora B ◽

Chromatid Cohesion

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Pericentromeric Sister Chromatid Cohesion Promotes Kinetochore Biorientation

Molecular Biology of the Cell ◽

10.1091/mbc.e09-04-0330 ◽

2009 ◽

Vol 20 (17) ◽

pp. 3818-3827 ◽

Cited By ~ 65

Author(s):

Tessie M. Ng ◽

William G. Waples ◽

Brigitte D. Lavoie ◽

Sue Biggins

Keyword(s):

Protein Kinase ◽

Genetic Analysis ◽

Chromosome Segregation ◽

Sister Chromatid ◽

Budding Yeast ◽

Sister Chromatid Cohesion ◽

Specific Role ◽

Aurora B ◽

Chromatid Cohesion ◽

Yeast Genes

Accurate chromosome segregation depends on sister kinetochores making bioriented attachments to microtubules from opposite poles. An essential regulator of biorientation is the Ipl1/Aurora B protein kinase that destabilizes improper microtubule–kinetochore attachments. To identify additional biorientation pathways, we performed a systematic genetic analysis between the ipl1-321 allele and all nonessential budding yeast genes. One of the mutants, mcm21Δ, precociously separates pericentromeres and this is associated with a defect in the binding of the Scc2 cohesin-loading factor at the centromere. Strikingly, Mcm21 becomes essential for biorientation when Ipl1 function is reduced, and this appears to be related to its role in pericentromeric cohesion. When pericentromeres are artificially tethered, Mcm21 is no longer needed for biorientation despite decreased Ipl1 activity. Taken together, these data reveal a specific role for pericentromeric linkage in ensuring kinetochore biorientation.

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Coordinated regulation of the ESCRT-III component CHMP4C by the chromosomal passenger complex and centralspindlin during cytokinesis

Open Biology ◽

10.1098/rsob.160248 ◽

2016 ◽

Vol 6 (10) ◽

pp. 160248 ◽

Cited By ~ 26

Author(s):

Luisa Capalbo ◽

Ioanna Mela ◽

Maria Alba Abad ◽

A. Arockia Jeyaprakash ◽

J. Michael Edwardson ◽

...

Keyword(s):

Atomic Force Microscopy ◽

Cell Division ◽

Aurora B ◽

Aurora B Kinase ◽

Chromosomal Passenger Complex ◽

Force Microscopy ◽

Daughter Cells ◽

Atomic Force ◽

Chromosomal Passenger

The chromosomal passenger complex (CPC)—composed of Aurora B kinase, Borealin, Survivin and INCENP—surveys the fidelity of genome segregation throughout cell division. The CPC has been proposed to prevent polyploidy by controlling the final separation (known as abscission) of the two daughter cells via regulation of the ESCRT-III CHMP4C component. The molecular details are, however, still unclear. Using atomic force microscopy, we show that CHMP4C binds to and remodels membranes in vitro . Borealin prevents the association of CHMP4C with membranes, whereas Aurora B interferes with CHMP4C's membrane remodelling activity. Moreover, we show that CHMP4C phosphorylation is not required for its assembly into spiral filaments at the abscission site and that two distinctly localized pools of phosphorylated CHMP4C exist during cytokinesis. We also characterized the CHMP4C interactome in telophase cells and show that the centralspindlin complex associates preferentially with unphosphorylated CHMP4C in cytokinesis. Our findings indicate that gradual dephosphorylation of CHMP4C triggers a ‘relay’ mechanism between the CPC and centralspindlin that regulates the timely distribution and activation of CHMP4C for the execution of abscission.

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EB1 enables spindle microtubules to regulate centromeric recruitment of Aurora B

The Journal of Cell Biology ◽

10.1083/jcb.201307119 ◽

2014 ◽

Vol 204 (6) ◽

pp. 947-963 ◽

Cited By ~ 38

Author(s):

Budhaditya Banerjee ◽

Cortney A. Kestner ◽

P. Todd Stukenberg

Keyword(s):

Mitotic Chromosome ◽

Histone H3 ◽

Aurora B ◽

Dependent Manner ◽

Histone H2a ◽

Aurora B Kinase ◽

Chromosomal Passenger Complex ◽

Checkpoint Signaling ◽

Chromosomal Passenger ◽

Spindle Microtubules

The Aurora B kinase coordinates kinetochore–microtubule attachments with spindle checkpoint signaling on each mitotic chromosome. We find that EB1, a microtubule plus end–tracking protein, is required to enrich Aurora B at inner centromeres in a microtubule-dependent manner. This regulates phosphorylation of both kinetochore and chromatin substrates. EB1 regulates the histone phosphorylation marks (histone H2A phospho-Thr120 and histone H3 phospho-Thr3) that localize Aurora B. The chromosomal passenger complex containing Aurora B can be found on a subset of spindle microtubules that exist near prometaphase kinetochores, known as preformed K-fibers (kinetochore fibers). Our data suggest that EB1 enables the spindle microtubules to regulate the phosphorylation of kinetochores through recruitment of the Aurora B kinase.

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