scholarly journals Aurora A promotes chromosome congression by activating the condensin-dependent pool of KIF4A

2019 ◽  
Author(s):  
Elena Poser ◽  
Renaud Caous ◽  
Ulrike Gruneberg ◽  
Francis A. Barr
Keyword(s):  
Metaphase Plate ◽  
Aurora Kinase ◽  
Chromosome Condensation ◽  
Aurora B ◽  
Aurora A ◽  
Specific Point ◽  
Aurora Kinases ◽  
Central Spindle ◽  
Spindle Poles ◽  
Chromosome Congression

AbstractAurora kinases create phosphorylation gradients within the spindle during prometaphase and anaphase. These locally regulate factors that promote spindle organisation, chromosome condensation and movement, and cytokinesis. We show that one such factor is the kinesin KIF4A, which is present along the chromosome axes throughout mitosis and the central spindle in anaphase. These two pools of KIF4A depend on condensin I and PRC1, respectively. Previous work has shown KIF4A is activated by Aurora B at the anaphase central spindle. However, whether or not chromosome-associated KIF4A bound to condensin I is regulated by Aurora kinases remain unclear. To determine the roles of the two different pools of KIF4A, we generated specific point mutants that are unable to interact with either condensin I or PRC1, or are deficient for Aurora kinase regulation. By analysing these mutants, we show that Aurora kinases phosphorylate the condensin I dependent pool of KIF4A and thus actively promote chromosome congression from the spindle poles to the metaphase plate.

scholarly journals Aurora A promotes chromosome congression by activating the condensin-dependent pool of KIF4A

2019 ◽  
Vol 219 (2) ◽  
Author(s):  
Elena Poser ◽  
Renaud Caous ◽  
Ulrike Gruneberg ◽  
Francis A. Barr
Keyword(s):  
Metaphase Plate ◽  
Aurora Kinase ◽  
Chromosome Condensation ◽  
Aurora B ◽  
Aurora A ◽  
Specific Point ◽  
Aurora Kinases ◽  
Central Spindle ◽  
Spindle Poles ◽  
Chromosome Congression

Aurora kinases create phosphorylation gradients within the spindle during prometaphase and anaphase, thereby locally regulating factors that promote spindle organization, chromosome condensation and movement, and cytokinesis. We show that one such factor is the kinesin KIF4A, which is present along the chromosome axes throughout mitosis and the central spindle in anaphase. These two pools of KIF4A depend on condensin I and PRC1, respectively. Previous work has shown KIF4A is activated by Aurora B at the anaphase central spindle. However, whether or not chromosome-associated KIF4A bound to condensin I is regulated by Aurora kinases remain unclear. To determine the roles of the two different pools of KIF4A, we generated specific point mutants that are unable to interact with either condensin I or PRC1 or are deficient for Aurora kinase regulation. By analyzing these mutants, we show that Aurora A phosphorylates the condensin I–dependent pool of KIF4A and thus actively promotes chromosome congression from the spindle poles to the metaphase plate.

scholarly journals Dictyostelium Aurora Kinase Has Properties of both Aurora A and Aurora B Kinases

2008 ◽  
Vol 7 (5) ◽  
pp. 894-905 ◽  
Author(s):  
Hui Li ◽  
Qian Chen ◽  
Markus Kaller ◽  
Wolfgang Nellen ◽  
Ralph Gräf ◽  
...  
Keyword(s):  
Myosin Ii ◽  
Aurora Kinase ◽  
Equatorial Region ◽  
Aurora B ◽  
Cleavage Furrow ◽  
Aurora A ◽  
Animal Cells ◽  
Aurora Kinases ◽  
Spindle Poles ◽  
Early Mitosis

ABSTRACT Aurora kinases are highly conserved proteins with important roles in mitosis. Metazoans contain two kinases, Aurora A and B, which contribute distinct functions at the spindle poles and the equatorial region respectively. It is not currently known whether the specialized functions of the two kinases arose after their duplication in animal cells or were already present in their ancestral kinase. We show that Dictyostelium discoideum contains a single Aurora kinase, DdAurora, that displays characteristics of both Aurora A and B. Like Aurora A, DdAurora has an extended N-terminal domain with an A-box sequence and localizes at the spindle poles during early mitosis. Like Aurora B, DdAurora binds to its partner DdINCENP and localizes on centromeres at metaphase, the central spindle during anaphase, and the cleavage furrow at the end of cytokinesis. DdAurora also has several unusual properties. DdAurora remains associated with centromeres in anaphase, and this association does not require an interaction with DdINCENP. DdAurora then localizes at the cleavage furrow, but only at the end of cytokinesis. This localization is dependent on DdINCENP and the motor proteins Kif12 and myosin II. Thus, DdAurora may represent the ancestral kinase that gave rise to the different Aurora kinases in animals and also those in other organisms.

scholarly journals A single starfish Aurora kinase performs the combined functions of Aurora-A and Aurora-B in human cells

Development ◽  
2010 ◽  
Vol 137 (23) ◽  
pp. e2308-e2308
Author(s):  
Y. Abe ◽  
Y. Abe ◽  
E. Okumura ◽  
T. Hosoya ◽  
T. Hirota ◽  
...  
Keyword(s):  
Aurora Kinase ◽  
Human Cells ◽  
Aurora B ◽  
Aurora A

scholarly journals A single starfish Aurora kinase performs the combined functions of Aurora-A and Aurora-B in human cells

2010 ◽  
Vol 123 (22) ◽  
pp. 3978-3988 ◽  
Author(s):  
Y. Abe ◽  
E. Okumura ◽  
T. Hosoya ◽  
T. Hirota ◽  
T. Kishimoto
Keyword(s):  
Aurora Kinase ◽  
Human Cells ◽  
Aurora B ◽  
Aurora A

scholarly journals The association of Plk1 with the astrin–kinastrin complex promotes formation and maintenance of a metaphase plate

2020 ◽  
Vol 134 (1) ◽  
pp. jcs251025
Author(s):  
Zoë Geraghty ◽  
Christina Barnard ◽  
Pelin Uluocak ◽  
Ulrike Gruneberg
Keyword(s):  
Molecular Mechanisms ◽  
Metaphase Plate ◽  
Direct Interaction ◽  
Mitotic Chromosomes ◽  
Spindle Formation ◽  
Bipolar Spindle ◽  
Mitotic Kinase ◽  
Spindle Poles ◽  
Chromosome Congression ◽  
Chromosome Alignment

ABSTRACTErrors in mitotic chromosome segregation can lead to DNA damage and aneuploidy, both hallmarks of cancer. To achieve synchronous error-free segregation, mitotic chromosomes must align at the metaphase plate with stable amphitelic attachments to microtubules emanating from opposing spindle poles. The astrin–kinastrin (astrin is also known as SPAG5 and kinastrin as SKAP) complex, also containing DYNLL1 and MYCBP, is a spindle and kinetochore protein complex with important roles in bipolar spindle formation, chromosome alignment and microtubule–kinetochore attachment. However, the molecular mechanisms by which astrin–kinastrin fulfils these diverse roles are not fully understood. Here, we characterise a direct interaction between astrin and the mitotic kinase Plk1. We identify the Plk1-binding site on astrin as well as four Plk1 phosphorylation sites on astrin. Regulation of astrin by Plk1 is dispensable for bipolar spindle formation and bulk chromosome congression, but promotes stable microtubule–kinetochore attachments and metaphase plate maintenance. It is known that Plk1 activity is required for effective microtubule–kinetochore attachment formation, and we suggest that astrin phosphorylation by Plk1 contributes to this process.

scholarly journals A single amino acid change converts Aurora-A into Aurora-B-like kinase in terms of partner specificity and cellular function

2009 ◽  
Vol 106 (17) ◽  
pp. 6939-6944 ◽  
Author(s):  
Jingyan Fu ◽  
Minglei Bian ◽  
Junjun Liu ◽  
Qing Jiang ◽  
Chuanmao Zhang
Keyword(s):  
Amino Acid ◽  
Aurora Kinase ◽  
Single Amino Acid ◽  
Aurora B ◽  
Aurora A ◽  
Single Amino Acid Residue ◽  
Single Amino Acid Change ◽  
Equivalent Residue ◽  
And Function

Aurora kinase-A and -B are key regulators of the cell cycle and tumorigenesis. It has remained a mystery why these 2 Aurora kinases, although highly similar in protein sequence and structure, are distinct in subcellular localization and function. Here, we report the striking finding that a single amino acid residue is responsible for these differences. We replaced the Gly-198 of Aurora-A with the equivalent residue Asn-142 of Aurora-B and found that in HeLa cells, Aurora-AG198N was recruited to the inner centromere in metaphase and the midzone in anaphase, reminiscent of the Aurora-B localization. Moreover, Aurora-AG198N compensated for the loss of Aurora-B in chromosome misalignment and cell premature exit from mitosis. Furthermore, Aurora-AG198N formed a complex with the Aurora-B partners, INCENP and Survivin, and its localization depended on this interaction. Aurora-AG198N phosphorylated the Aurora-B substrates INCENP and Survivin in vitro. Therefore, we propose that the presence of Gly or Asn at a single site assigns Aurora-A and -B to their respective partners and thus to their distinctive subcellular localizations and functions.

TheS. pombeaurora-related kinase Ark1 associates with mitotic structures in a stage dependent manner and is required for chromosome segregation

2001 ◽  
Vol 114 (24) ◽  
pp. 4371-4384 ◽  
Author(s):  
Janni Petersen ◽  
Jeannie Paris ◽  
Martin Willer ◽  
Michel Philippe ◽  
Iain M. Hagan
Keyword(s):  
Fission Yeast ◽  
Histone H3 ◽  
Central Zone ◽  
Chromosome Condensation ◽  
Yeast Cells ◽  
Aurora B ◽  
Dependent Manner ◽  
Aurora A ◽  
Spindle Formation

Metazoans contain three aurora-related kinases. Aurora A is required for spindle formation while aurora B is required for chromosome condensation and cytokinesis. Less is known about the function of aurora C. S. pombe contains a single aurora-related kinase, Ark1. Although Ark1 protein levels remained constant as cells progressed through the mitotic cell cycle, its distribution altered during mitosis and meiosis. Throughout G2 Ark1 was concentrated in one to three nuclear foci that were not associated with the spindle pole body/centromere complex. Following commitment to mitosis Ark1 associated with chromatin and was particularly concentrated at several sites including kinetochores/centromeres. Kinetochore/centromere association diminished during anaphase A, after which it was distributed along the spindle. The protein became restricted to a small central zone that transiently enlarged as the spindle extended. As in many other systems mitotic fission yeast cells exhibit a much greater degree of phosphorylation of serine 10 of histone H3 than interphase cells. A number of studies have linked this modification with chromosome condensation. Ark1 immuno-precipitates phosphorylated serine 10 of histone H3 in vitro. This activity was highest in mitotic extracts. The absence of the histone H3 phospho-serine 10 epitope from mitotic cells in which the ark1+ gene had been deleted (ark1.Δ1); the inability of these cells to resolve their chromosomes during anaphase and the co-localisation of this phospho-epitope with Ark1 early in mitosis, all suggest that Ark1 phosphorylates serine 10 of histone H3 in vivo. ark1.Δ1 cells also exhibited a reduction in kinetochore activity and a minor defect in spindle formation. Thus the enzyme activity, localisation and phenotype arising from our manipulations of this single fission yeast aurora kinase family member suggest that this single kinase is executing functions that are separately implemented by distinct aurora A and aurora B kinases in higher systems.

scholarly journals Drosophila Aurora A kinase is required to localize D-TACC to centrosomes and to regulate astral microtubules

2002 ◽  
Vol 156 (3) ◽  
pp. 437-451 ◽  
Author(s):  
Régis Giet ◽  
Doris McLean ◽  
Simon Descamps ◽  
Michael J. Lee ◽  
Jordan W. Raff ◽  
...  
Keyword(s):  
Coiled Coil ◽  
Aurora Kinase ◽  
The Other ◽  
S2 Cells ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Spindle Poles

Disruption of the function of the A-type Aurora kinase of Drosophila by mutation or RNAi leads to a reduction in the length of astral microtubules in syncytial embryos, larval neuroblasts, and cultured S2 cells. In neuroblasts, it can also lead to loss of an organized centrosome and its associated aster from one of the spindle poles, whereas the centrosome at the other pole has multiple centrioles. When centrosomes are present at the poles of aurA mutants or aurA RNAi spindles, they retain many antigens but are missing the Drosophila counterpart of mammalian transforming acidic coiled coil (TACC) proteins, D-TACC. We show that a subpopulation of the total Aurora A is present in a complex with D-TACC, which is a substrate for the kinase. We propose that one of the functions of Aurora A kinase is to direct centrosomal organization such that D-TACC complexed to the MSPS/XMAP215 microtubule-associated protein may be recruited, and thus modulate the behavior of astral microtubules.

scholarly journals Inhibition of Aurora A and Aurora B Is Required for the Sensitivity of HPV-Driven Cervical Cancers to Aurora Kinase Inhibitors

2017 ◽  
Vol 16 (9) ◽  
pp. 1934-1941 ◽  
Author(s):  
David Martin ◽  
Sora Fallaha ◽  
Martina Proctor ◽  
Alexander Stevenson ◽  
Lewis Perrin ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Aurora Kinase ◽  
Aurora B ◽  
Aurora A ◽  
Cervical Cancers ◽  
Aurora Kinase Inhibitors
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