scholarly journals Direct Nucleosome Binding of Borealin Secures Chromosome Association and Function of the Chromosomal Passenger complex

2019 ◽  
Author(s):  
M. A. Abad ◽  
J. G. Ruppert ◽  
L. Buzuk ◽  
M. Wear ◽  
J. Zou ◽  
...  
Keyword(s):  
Cell Division ◽  
Chromosome Segregation ◽  
Chromosome Association ◽  
Aurora B ◽  
Multifaceted Approach ◽  
Chromosomal Passenger Complex ◽  
Chromosome Congression ◽  
Chromosomal Passenger ◽  
And Function ◽  
Nucleosome Binding

SummaryChromosome association of the Chromosomal Passenger Complex (CPC; consisting of Borealin, Survivin, INCENP and the Aurora B kinase) is essential to achieve error-free chromosome segregation during cell division. Hence, understanding the mechanisms driving the chromosome association of the CPC is of paramount importance. Here using a multifaceted approach, we show that the CPC binds nucleosomes through a multivalent interaction predominantly involving Borealin. Strikingly, Survivin, previously suggested to target the CPC to centromeres [1–3] failed to bind nucleosomes on its own and requires Borealin and INCENP for its binding. Disrupting Borealin-nucleosome interactions excluded the CPC from chromosomes and caused chromosome congression defects. We also show that Borealin-mediated chromosome association of the CPC is critical for Haspin- and Bub1-mediated centromere enrichment of the CPC and works upstream of the latter. Our work thus establishes Borealin as a master regulator determining the chromosome association and function of the CPC.

scholarly journals Borealin–nucleosome interaction secures chromosome association of the chromosomal passenger complex

2019 ◽  
Vol 218 (12) ◽  
pp. 3912-3925 ◽  
Author(s):  
Maria A. Abad ◽  
Jan G. Ruppert ◽  
Lana Buzuk ◽  
Martin Wear ◽  
Juan Zou ◽  
...  
Keyword(s):  
Cell Division ◽  
Chromosome Segregation ◽  
Chromosome Association ◽  
Aurora B ◽  
Master Regulator ◽  
Multifaceted Approach ◽  
Chromosomal Passenger Complex ◽  
Chromosome Congression ◽  
Chromosomal Passenger ◽  
And Function

Chromosome association of the chromosomal passenger complex (CPC; consisting of Borealin, Survivin, INCENP, and the Aurora B kinase) is essential to achieve error-free chromosome segregation during cell division. Hence, understanding the mechanisms driving the chromosome association of the CPC is of paramount importance. Here using a multifaceted approach, we show that the CPC binds nucleosomes through a multivalent interaction predominantly involving Borealin. Strikingly, Survivin, previously suggested to target the CPC to centromeres, failed to bind nucleosomes on its own and requires Borealin and INCENP for its binding. Disrupting Borealin–nucleosome interactions excluded the CPC from chromosomes and caused chromosome congression defects. We also show that Borealin-mediated chromosome association of the CPC is critical for Haspin- and Bub1-mediated centromere enrichment of the CPC and works upstream of the latter. Our work thus establishes Borealin as a master regulator determining the chromosome association and function of the CPC.

scholarly journals The chromosomal passenger complex: guiding Aurora-B through mitosis

2006 ◽  
Vol 173 (6) ◽  
pp. 833-837 ◽  
Author(s):  
Gerben Vader ◽  
René H. Medema ◽  
Susanne M.A. Lens
Keyword(s):  
Cell Division ◽  
Histone Modification ◽  
Posttranslational Modifications ◽  
Molecular Mechanisms ◽  
Aurora B ◽  
Chromosomal Passenger Complex ◽  
Precise Control ◽  
Chromosome Alignment ◽  
Chromosomal Passenger ◽  
And Function

During mitosis, the chromosomal passenger complex (CPC) orchestrates highly different processes, such as chromosome alignment, histone modification, and cytokinesis. Proper and timely localization of this complex is the key to precise control over the enzymatic core of the CPC, the Aurora-B kinase. We discuss the molecular mechanisms by which the CPC members direct the dynamic localization of the complex throughout cell division. Also, we summarize posttranslational modifications that occur on the CPC and discuss their roles in regulating localization and function of this mitotic complex.

scholarly journals Phosphorylation at serine 331 is required for Aurora B activation

2011 ◽  
Vol 195 (3) ◽  
pp. 449-466 ◽  
Author(s):  
Eleni Petsalaki ◽  
Tonia Akoumianaki ◽  
Elizabeth J. Black ◽  
David A.F. Gillespie ◽  
George Zachos
Keyword(s):  
Cell Division ◽  
Kinase Activity ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Chromosomal Passenger Complex ◽  
Chromosome Missegregation ◽  
Mitotic Delay ◽  
Chromosomal Passenger ◽  
Spontaneous Chromosome ◽  
Chk1 Kinase

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.

scholarly journals The chromosomal passenger complex controls the function of endosomal sorting complex required for transport-III Snf7 proteins during cytokinesis

Open Biology ◽  
2012 ◽  
Vol 2 (5) ◽  
pp. 120070 ◽  
Author(s):  
Luisa Capalbo ◽  
Emilie Montembault ◽  
Tetsuya Takeda ◽  
Zuni I. Bassi ◽  
David M. Glover ◽  
...  
Keyword(s):  
Cell Division ◽  
Molecular Basis ◽  
Cleavage Site ◽  
Human Cells ◽  
Membrane Association ◽  
Aurora B ◽  
Chromosomal Passenger Complex ◽  
Endosomal Sorting ◽  
Daughter Cells ◽  
Chromosomal Passenger

Summary Cytokinesis controls the proper segregation of nuclear and cytoplasmic materials at the end of cell division. The chromosomal passenger complex (CPC) has been proposed to monitor the final separation of the two daughter cells at the end of cytokinesis in order to prevent cell abscission in the presence of DNA at the cleavage site, but the precise molecular basis for this is unclear. Recent studies indicate that abscission could be mediated by the assembly of filaments comprising components of the endosomal sorting complex required for transport-III (ESCRT-III). Here, we show that the CPC subunit Borealin interacts directly with the Snf7 components of ESCRT-III in both Drosophila and human cells. Moreover, we find that the CPC's catalytic subunit, Aurora B kinase, phosphorylates one of the three human Snf7 paralogues—CHMP4C—in its C-terminal tail, a region known to regulate its ability to form polymers and associate with membranes. Phosphorylation at these sites appears essential for CHMP4C function because their mutation leads to cytokinesis defects. We propose that CPC controls abscission timing through inhibition of ESCRT-III Snf7 polymerization and membrane association using two concurrent mechanisms: interaction of its Borealin component with Snf7 proteins and phosphorylation of CHMP4C by Aurora B.

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

Open Biology ◽  
2016 ◽  
Vol 6 (10) ◽  
pp. 160248 ◽  
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.

Functionality of the chromosomal passenger complex in cancer

2015 ◽  
Vol 43 (1) ◽  
pp. 23-32 ◽  
Author(s):  
Sanne Hindriksen ◽  
Amanda Meppelink ◽  
Susanne M.A. Lens
Keyword(s):  
Cell Division ◽  
Chromosome Segregation ◽  
Chromosomal Instability ◽  
Cultured Cells ◽  
Present Review ◽  
Next Generation ◽  
Chromosomal Passenger Complex ◽  
Human Cancers ◽  
Chromosomal Passenger ◽  
Ploidy Status

The evolutionary conserved chromosomal passenger complex (CPC) is essential for faithful transmission of the genome during cell division. Perturbation of this complex in cultured cells gives rise to chromosome segregation errors and cytokinesis failure and as a consequence the ploidy status of the next generation of cells is changed. Aneuploidy and chromosomal instability (CIN) is observed in many human cancers, but whether this may be caused by deregulation of the CPC is unknown. In the present review, we discuss if and how a dysfunctional CPC could contribute to CIN in cancer.

scholarly journals Nbl1p: A Borealin/Dasra/CSC-1-like Protein Essential for Aurora/Ipl1 Complex Function and Integrity in Saccharomyces cerevisiae

2009 ◽  
Vol 20 (6) ◽  
pp. 1772-1784 ◽  
Author(s):  
Yuko Nakajima ◽  
Randall G. Tyers ◽  
Catherine C.L. Wong ◽  
John R. Yates ◽  
David G. Drubin ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Complex Function ◽  
Aurora Kinase ◽  
Aurora B ◽  
Protein Structure Modeling ◽  
Homology Searching ◽  
Chromosomal Passenger ◽  
And Function ◽  
Computational Analyses ◽  
Related Proteins

The Aurora kinase complex, also called the chromosomal passenger complex (CPC), is essential for faithful chromosome segregation and completion of cell division. In Fungi and Animalia, this complex consists of the kinase Aurora B/AIR-2/Ipl1p, INCENP/ICP-1/Sli15p, and Survivin/BIR-1/Bir1p. A fourth subunit, Borealin/Dasra/CSC-1, is required for CPC targeting to centromeres and central spindles and has only been found in Animalia. Here we identified a new core component of the CPC in budding yeast, Nbl1p. NBL1 is essential for viability and nbl1 mutations cause chromosome missegregation and lagging chromosomes. Nbl1p colocalizes and copurifies with the CPC, and it is essential for CPC localization, stability, integrity, and function. Nbl1p is related to the N-terminus of Borealin/Dasra/CSC-1 and is similarly involved in connecting the other CPC subunits. Distant homology searching identified nearly 200, mostly unannotated, Borealin/Dasra/CSC-1–related proteins from nearly 150 species within Fungi and Animalia. Analysis of the sequence of these proteins, combined with comparative protein structure modeling of Bir1p-Nbl1p-Sli15p using the crystal structure of the human Survivin–Borealin–INCENP complex, revealed a striking structural conservation across a broad range of species. Our biological and computational analyses therefore establish that the fundamental design of the CPC is conserved from Fungi to Animalia.

scholarly journals Cross-regulation between Aurora B and Citron kinase controls midbody architecture in cytokinesis

Open Biology ◽  
2016 ◽  
Vol 6 (3) ◽  
pp. 160019 ◽  
Author(s):  
Callum McKenzie ◽  
Zuni I. Bassi ◽  
Janusz Debski ◽  
Marco Gottardo ◽  
Giuliano Callaini ◽  
...  
Keyword(s):  
Cell Division ◽  
Molecular Mechanisms ◽  
Coiled Coil ◽  
Aurora B ◽  
Intercellular Bridge ◽  
Daughter Cells ◽  
Chromosomal Passenger ◽  
Citron Kinase ◽  
And Function ◽  
First Time

Cytokinesis culminates in the final separation, or abscission, of the two daughter cells at the end of cell division. Abscission relies on an organelle, the midbody, which forms at the intercellular bridge and is composed of various proteins arranged in a precise stereotypic pattern. The molecular mechanisms controlling midbody organization and function, however, are obscure. Here we show that proper midbody architecture requires cross-regulation between two cell division kinases, Citron kinase (CIT-K) and Aurora B, the kinase component of the chromosomal passenger complex (CPC). CIT-K interacts directly with three CPC components and is required for proper midbody architecture and the orderly arrangement of midbody proteins, including the CPC. In addition, we show that CIT-K promotes Aurora B activity through phosphorylation of the INCENP CPC subunit at the TSS motif. In turn, Aurora B controls CIT-K localization and association with its central spindle partners through phosphorylation of CIT-K's coiled coil domain. Our results identify, for the first time, a cross-regulatory mechanism between two kinases during cytokinesis, which is crucial for establishing the stereotyped organization of midbody proteins.

scholarly journals Liquid-liquid phase separation of the chromosomal passenger complex drives parallel bundling of midzone microtubules

2022 ◽  
Author(s):  
Ewa Niedzialkowska ◽  
Tan M Truong ◽  
Luke A Eldredge ◽  
Stefanie Redemann ◽  
Denis Chretien ◽  
...  
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Chromosome Segregation ◽  
Dynamic Structure ◽  
Liquid Phase Separation ◽  
Chromosomal Passenger Complex ◽  
Chromosomal Passenger ◽  
Spindle Midzone ◽  
Liquid Liquid Phase Separation

The spindle midzone is a dynamic structure that forms during anaphase, mediates chromosome segregation, and provides a signaling platform to position the cleavage furrow. The spindle midzone comprises two antiparallel bundles of microtubules (MTs) but the process of their formation is poorly understood. Here, we show that the Chromosomal Passenger Complex (CPC) undergoes liquid-liquid phase separation (LLPS) to generate parallel MT bundles in vitro when incubated with free tubulin and GTP. MT bundles emerge from CPC droplets with protruding minus-ends that then grow into long, tapered MT structures. During this growth, the CPC in condensates apparently reorganize to coat and bundle the resulting MT structures. CPC mutants attenuated for LLPS or MT binding prevented the generation of parallel MT bundles in vitro and reduced the number of MTs present at spindle midzones in HeLa cells. Our data uncovers a kinase-independent function of the CPC and provides models for how cells generate parallel-bundled MT structures that are important for the assembly of the mitotic spindle.

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