scholarly journals Bistability of a coupled Aurora B kinase-phosphatase system in cell division

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Anatoly V Zaytsev ◽  
Dario Segura-Peña ◽  
Maxim Godzi ◽  
Abram Calderon ◽  
Edward R Ballister ◽  
...  
Keyword(s):  
Cell Division ◽  
Regulatory Mechanisms ◽  
Live Cells ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Bistable Behavior ◽  
Spatial Regulation ◽  
Two Component ◽  
Phosphatase System ◽  
Kinase A

Aurora B kinase, a key regulator of cell division, localizes to specific cellular locations, but the regulatory mechanisms responsible for phosphorylation of substrates located remotely from kinase enrichment sites are unclear. Here, we provide evidence that this activity at a distance depends on both sites of high kinase concentration and the bistability of a coupled kinase-phosphatase system. We reconstitute this bistable behavior and hysteresis using purified components to reveal co-existence of distinct high and low Aurora B activity states, sustained by a two-component kinase autoactivation mechanism. Furthermore, we demonstrate these non-linear regimes in live cells using a FRET-based phosphorylation sensor, and provide a mechanistic theoretical model for spatial regulation of Aurora B phosphorylation. We propose that bistability of an Aurora B-phosphatase system underlies formation of spatial phosphorylation patterns, which are generated and spread from sites of kinase autoactivation, thereby regulating cell division.

scholarly journals Author response: Bistability of a coupled Aurora B kinase-phosphatase system in cell division

2015 ◽  
Author(s):  
Anatoly V Zaytsev ◽  
Dario Segura-Peña ◽  
Maxim Godzi ◽  
Abram Calderon ◽  
Edward R Ballister ◽  
...  
Keyword(s):  
Cell Division ◽  
Author Response ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Phosphatase System

scholarly journals A complex containing the Sm protein CAR-1 and the RNA helicase CGH-1 is required for embryonic cytokinesis in Caenorhabditis elegans

2005 ◽  
Vol 171 (2) ◽  
pp. 267-279 ◽  
Author(s):  
Anjon Audhya ◽  
Francie Hyndman ◽  
Ian X. McLeod ◽  
Amy S. Maddox ◽  
John R. Yates ◽  
...  
Keyword(s):  
Cell Division ◽  
Caenorhabditis Elegans ◽  
Rna Binding ◽  
Rna Binding Protein ◽  
Rna Helicase ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Daughter Cells ◽  
Sm Protein ◽  
Spindle Structure

Cytokinesis completes cell division and partitions the contents of one cell to the two daughter cells. Here we characterize CAR-1, a predicted RNA binding protein that is implicated in cytokinesis. CAR-1 localizes to germline-specific RNA-containing particles and copurifies with the essential RNA helicase, CGH-1, in an RNA-dependent fashion. The atypical Sm domain of CAR-1, which directly binds RNA, is dispensable for CAR-1 localization, but is critical for its function. Inhibition of CAR-1 by RNA-mediated depletion or mutation results in a specific defect in embryonic cytokinesis. This cytokinesis failure likely results from an anaphase spindle defect in which interzonal microtubule bundles that recruit Aurora B kinase and the kinesin, ZEN-4, fail to form between the separating chromosomes. Depletion of CGH-1 results in sterility, but partially depleted worms produce embryos that exhibit the CAR-1–depletion phenotype. Cumulatively, our results suggest that CAR-1 functions with CGH-1 to regulate a specific set of maternally loaded RNAs that is required for anaphase spindle structure and cytokinesis.

scholarly journals Endopolyploidy in irradiated p53-deficient tumour cell lines: Persistence of cell division activity in giant cells expressing Aurora-B kinase

2008 ◽  
Vol 32 (9) ◽  
pp. 1044-1056 ◽  
Author(s):  
Jekaterina Erenpreisa ◽  
Andrei Ivanov ◽  
Sally P. Wheatley ◽  
Elizabeth A. Kosmacek ◽  
Fiorenza Ianzini ◽  
...  
Keyword(s):  
Cell Division ◽  
Cell Lines ◽  
Tumour Cell ◽  
Giant Cells ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Tumour Cell Lines

Frequent overexpression of aurora B kinase, a novel drug target, in non–small cell lung carcinoma patients

2006 ◽  
Vol 5 (11) ◽  
pp. 2905-2913 ◽  
Author(s):  
Barbara Vischioni ◽  
Joost J. Oudejans ◽  
Wim Vos ◽  
Jose A. Rodriguez ◽  
Giuseppe Giaccone
Keyword(s):  
Lung Carcinoma ◽  
Drug Target ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Aurora B ◽  
Small Cell Lung ◽  
Aurora B Kinase ◽  
Cell Lung Carcinoma ◽  
Novel Drug ◽  
Kinase A

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 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.

scholarly journals Relocation of Aurora B from centromeres to the central spindle at the metaphase to anaphase transition requires MKlp2

2004 ◽  
Vol 166 (2) ◽  
pp. 167-172 ◽  
Author(s):  
Ulrike Gruneberg ◽  
Rüdiger Neef ◽  
Reiko Honda ◽  
Erich A. Nigg ◽  
Francis A. Barr
Keyword(s):  
Chromosome Segregation ◽  
Aurora B ◽  
Dual Control ◽  
Aurora B Kinase ◽  
Central Spindle ◽  
Binding Partner ◽  
Mitotic Kinases ◽  
Spatial Regulation

Mitotic kinases of the Polo and Aurora families are key regulators of chromosome segregation and cytokinesis. Here, we have investigated the role of MKlp1 and MKlp2, two vertebrate mitotic kinesins essential for cytokinesis, in the spatial regulation of the Aurora B kinase. Previously, we have demonstrated that MKlp2 recruits Polo-like kinase 1 (Plk1) to the central spindle in anaphase. We now find that in MKlp2 but not MKlp1-depleted cells the Aurora B–INCENP complex remains at the centromeres and fails to relocate to the central spindle. MKlp2 exerts dual control over Aurora B localization, because it is a binding partner for Aurora B, and furthermore for the phosphatase Cdc14A. Cdc14A can dephosphorylate INCENP and may contribute to its relocation to the central spindle in anaphase. We propose that MKlp2 is involved in the localization of Plk1, Aurora B, and Cdc14A to the central spindle during anaphase, and that the integration of signaling by these proteins is necessary for proper cytokinesis.

Aurora B kinase: a potential drug target for cancer therapy

2021 ◽  
Author(s):  
Azaj Ahmed ◽  
Anas Shamsi ◽  
Taj Mohammad ◽  
Gulam Mustafa Hasan ◽  
Asimul Islam ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Drug Target ◽  
Aurora B ◽  
Potential Drug Target ◽  
Potential Drug ◽  
Aurora B Kinase ◽  
Kinase A
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