Aurora kinase-A regulates kinetochore/chromatin associated microtubule assembly in human cells

Katayama, Hiroshi; Sasai, Kaori; Kloc, Małgorzata; Brinkley, B. R.; Sen, Subrata

doi:10.4161/cc.7.17.6460

Cited by 60 publications

(66 citation statements)

References 55 publications

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“…To our surprise, recombinant Aurora-A, purified from either Escherichia coli or Sf21 insect cells, binds INCENP 826 -919 in a GST pull-down assay (Fig. 3E), and phosphorylates INCENP 826 -919 and Survivin in vitro (36), indicating the potential of Aurora-A to act like Aurora-B. Addition of TPX2 eliminates the interaction between Aurora-A and INCENP in the GST pull-down assay (Fig.…”

Section: Discussionmentioning

confidence: 99%

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

Bian

Liu

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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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-A G198N was recruited to the inner centromere in metaphase and the midzone in anaphase, reminiscent of the Aurora-B localization. Moreover, Aurora-A G198N compensated for the loss of Aurora-B in chromosome misalignment and cell premature exit from mitosis. Furthermore, Aurora-A G198N formed a complex with the Aurora-B partners, INCENP and Survivin, and its localization depended on this interaction. Aurora-A G198N 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.single amino acid mutation ͉ TPX2 ͉ INCENP ͉ Survivin

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Section: Discussionmentioning

confidence: 99%

“…Both INCENP 826 -919 and Survivin were phosphorylated by Aurora-A G198N , Aurora-B WT (Fig. 4A), and Aurora-A WT (36). To test whether Aurora-A G198N could be activated by INCENP as is Aurora-B, kinase assay was performed using MBP as the substrate.…”

Section: Aurora-a G198n Interacts With Incenp and Survivin And Its Lmentioning

confidence: 99%

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

Bian

Liu

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…1F) (15)(16)(17)(18). Moreover, knockdown of Aurora A, which functions upstream of TACC3 (19), clearly abolished the acentrosomal microtubule aster formation (Fig. 1G).…”

Section: Significancementioning

confidence: 99%

Self-assembly and sorting of acentrosomal microtubules by TACC3 facilitate kinetochore capture during the mitotic spindle assembly

Chen

Wang

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Kinetochore capture by dynamic kinetochore microtubule fibers (K fibers) is essential for proper chromosome alignment and accurate distribution of the replicated genome during cell division. Although this capture process has been extensively studied, the mechanisms underlying the initiation of this process and the proper formation of the K fibers remain largely unknown. Here we show that transforming acidic coiled-coil-containing protein 3 (TACC3) is essential for kinetochore capture and proper K-fiber formation in HeLa cells. To observe the assembly of acentrosomal microtubules more clearly, the cells were released from higher concentrations of nocodazole into zero or lower concentrations. We find that small acentrosomal TACC3-microtubule aster formation near the kinetochores and binding of the asters with the kinetochores are the initial steps of the kinetochore capture by the acentrosomal microtubules, and that the sorting of kinetochore-captured acentrosomal microtubules with centrosomal microtubules leads to the capture of kinetochore by centrosomal microtubules from both spindle poles. We demonstrate that the sorting of the TACC3-associated microtubules with the centrosomal microtubules is a crucial process for spindle assembly and chromosome movement. These findings, which are also supported in the unperturbed mitosis without nocodazole, reveal a critical TACC3-dependent acentrosomal microtubule nucleation and sorting process to regulate kinetochore-microtubule connections and provide deep insight into the mechanisms of mitotic spindle assembly and chromosome alignment.T o ensure proper segregation of the chromosomes into its two daughter cells during proliferation, the chromosomes of a mother cell must be captured by its assembling mitotic spindle through attachment of the chromosome kinetochores and the dynamic spindle microtubules (1). A "search-and-capture" model was proposed long ago, in which the dynamic spindle microtubules nucleated from the centrosomes search for and capture the chromosome kinetochores (2). Previous studies showed that the kinetochores are initially captured by the spindle-polenucleated microtubules with their lateral side (3, 4). Once captured, the kinetochores with their chromosomes are transported along the microtubules toward a spindle pole, and the microtubules shrink at their plus ends until the establishment of the end-on attachment (4, 5). However, this model is insufficient to explain the initial connection of the kinetochore and the spindle microtubules in the centrosome-independent spindle assembly process. Recent studies in Xenopus extracts indicated that microtubules are nucleated near the chromosomes and self-organize into a spindle (6). A new model for acentrosomal spindle assembly has been raised in mouse oocytes, in which self-organized microtubule organizing centers (MTOCs) replace the centrosome function (7). The somatic cells may also use the centrosome-independent pathway for their spindle assembly (8-10). In Drosophila cells, the centrosome-independent assem...

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“…Surprisingly, Mad1 levels were also reduced on polar chromosomes after inhibition of Aurora A kinase, indicating a role of Aurora A in the spatial regulation of kinetochore-microtubule attachments near the spindle poles. Indeed, Aurora A had been previously implicated in the stabilization of kinetochore-microtubule attachments, 49,50 which might be explained by the fact that Aurora A shares 70% identity of its catalytical domain with Aurora B 51 and that both kinases recognize almost identical consensus target motifs. 52 Thus, Aurora A and Aurora B might have overlapping functions in the correction of kinetochoremicrotubule attachments that are spatially regulated by their different localization (Aurora A being placed at the centrosomes and Aurora B at the centromeres), which is defined by their different binding partners.…”

Section: Dynein Prevents Prematurementioning

confidence: 99%

Dynein prevents erroneous kinetochore-microtubule attachments in mitosis

Barišić

Maiato

2015

Cell Cycle

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Aurora kinase-A regulates kinetochore/chromatin associated microtubule assembly in human cells

Cited by 60 publications

References 55 publications

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

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

Self-assembly and sorting of acentrosomal microtubules by TACC3 facilitate kinetochore capture during the mitotic spindle assembly

Dynein prevents erroneous kinetochore-microtubule attachments in mitosis

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