scholarly journals Nuclear localisation of Aurora-A: its regulation and significance for Aurora-A functions in cancer

Oncogene ◽  
2021 ◽  
Author(s):  
Francesco Davide Naso ◽  
Dalila Boi ◽  
Camilla Ascanelli ◽  
Georgiana Pamfil ◽  
Catherine Lindon ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cell Division ◽  
Chromosomal Instability ◽  
Gene Locus ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Post Translational Modifications ◽  
Independent Functions ◽  
Anti Cancer ◽  
Existing Data

AbstractThe Aurora-A kinase regulates cell division, by controlling centrosome biology and spindle assembly. Cancer cells often display elevated levels of the kinase, due to amplification of the gene locus, increased transcription or post-translational modifications. Several inhibitors of Aurora-A activity have been developed as anti-cancer agents and are under evaluation in clinical trials. Although the well-known mitotic roles of Aurora-A point at chromosomal instability, a hallmark of cancer, as a major link between Aurora-A overexpression and disease, recent evidence highlights the existence of non-mitotic functions of potential relevance. Here we focus on a nuclear-localised fraction of Aurora-A with oncogenic roles. Interestingly, this pool would identify not only non-mitotic, but also kinase-independent functions of the kinase. We review existing data in the literature and databases, examining potential links between Aurora-A stabilisation and localisation, and discuss them in the perspective of a more effective targeting of Aurora-A in cancer therapy.

scholarly journals The nucleoporin Nup205/NPP-3 is lost near centrosomes at mitotic onset and can modulate the timing of this process in Caenorhabditis elegans embryos

2012 ◽  
Vol 23 (16) ◽  
pp. 3111-3121 ◽  
Author(s):  
Virginie Hachet ◽  
Coralie Busso ◽  
Mika Toya ◽  
Asako Sugimoto ◽  
Peter Askjaer ◽  
...  
Keyword(s):  
Cell Division ◽  
Rna Interference ◽  
Caenorhabditis Elegans ◽  
Nuclear Envelope ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Time And Space ◽  
Local Loss ◽  
Necessary And Sufficient

Regulation of mitosis in time and space is critical for proper cell division. We conducted an RNA interference–based modifier screen to identify novel regulators of mitosis in Caenorhabditis elegans embryos. Of particular interest, this screen revealed that the Nup205 nucleoporin NPP-3 can negatively modulate the timing of mitotic onset. Furthermore, we discovered that NPP-3 and nucleoporins that are associated with it are lost from the nuclear envelope (NE) in the vicinity of centrosomes at the onset of mitosis. We demonstrate that centrosomes are both necessary and sufficient for NPP-3 local loss, which also requires the activity of the Aurora-A kinase AIR-1. Our findings taken together support a model in which centrosomes and AIR-1 promote timely onset of mitosis by locally removing NPP-3 and associated nucleoporins from the NE.

Aurora a kinase (AURKA) is required for male germline maintenance and regulates sperm motility in the mouse

2021 ◽  
Author(s):  
William C Lester ◽  
Taylor Johnson ◽  
Ben Hale ◽  
Nicholas Serra ◽  
Brian Elgart ◽  
...  
Keyword(s):  
Cell Division ◽  
Sperm Count ◽  
Mitotic Cell ◽  
Vital Role ◽  
Conditional Knockout ◽  
Testis Size ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Mitotic Kinase ◽  
Knockout Animals

Abstract Aurora A kinase (AURKA) is an important regulator of cell division and is required for assembly of the mitotic spindle. We recently reported the unusual finding that this mitotic kinase is also found on the sperm flagellum. To determine its requirement in spermatogenesis, we generated conditional knockout animals with deletion of the Aurka gene in either spermatogonia or spermatocytes to assess its role in mitotic and postmitotic cells, respectively. Deletion of Aurka in spermatogonia resulted in disappearance of all developing germ cells in the testis, as expected given its vital role in mitotic cell division. Deletion of Aurka in spermatocytes reduced testis size, sperm count, and fertility, indicating disruption of meiosis or an effect on spermiogenesis in developing mice. Interestingly, deletion of Aurka in spermatocytes increased apoptosis in spermatocytes along with an increase in the percentage of sperm with abnormal morphology. Despite the increase in abnormal sperm, sperm from spermatocyte Aurka knockout mice displayed increased progressive motility. In addition, sperm lysate prepared from Aurka knockout animals had decreased protein phosphatase 1 (PP1) activity. Together, our results show that AURKA plays multiple roles in spermatogenesis, from mitotic divisions of spermatogonia to sperm morphology and motility.

scholarly journals Defining the Anti-Cancer Activity of Tricarbonyl Rhenium Complexes: Induction of G2/M Cell Cycle Arrest and Blockade of Aurora-A Kinase Phosphorylation

2017 ◽  
Vol 23 (27) ◽  
pp. 6518-6521 ◽  
Author(s):  
Peter V. Simpson ◽  
Ilaria Casari ◽  
Silvano Paternoster ◽  
Brian W. Skelton ◽  
Marco Falasca ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Aurora A Kinase ◽  
Aurora A ◽  
M Cell ◽  
Rhenium Complexes ◽  
Cycle Arrest ◽  
Anti Cancer ◽  
Kinase Phosphorylation ◽  
Cancer Activity

Suppression of multiple processes relevant to cancer progression by benzyl isothiocyanate may result from the inhibition of Aurora A kinase activity

2020 ◽  
Vol 11 (10) ◽  
pp. 9010-9019
Author(s):  
Tzu-Tung Yu ◽  
Meng-Ya Chang ◽  
Yi-Jen Hsieh ◽  
Chih-Jui Chang
Keyword(s):  
Cancer Progression ◽  
Kinase Activity ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Benzyl Isothiocyanate ◽  
Anti Cancer ◽  
Multiple Processes

The anti-cancer properties of BITC may result from the inhibition of Aurora A kinase activity.

scholarly journals Aurora A kinase (AURKA) in normal and pathological cell division

2012 ◽  
Vol 70 (4) ◽  
pp. 661-687 ◽  
Author(s):  
Anna S. Nikonova ◽  
Igor Astsaturov ◽  
Ilya G. Serebriiskii ◽  
Roland L. Dunbrack ◽  
Erica A. Golemis
Keyword(s):  
Cell Division ◽  
Aurora A Kinase ◽  
Aurora A

scholarly journals NDEL1 Phosphorylation by Aurora-A Kinase Is Essential for Centrosomal Maturation, Separation, and TACC3 Recruitment

2006 ◽  
Vol 27 (1) ◽  
pp. 352-367 ◽  
Author(s):  
Daisuke Mori ◽  
Yoshihisa Yano ◽  
Kazuhito Toyo-oka ◽  
Noriyuki Yoshida ◽  
Masami Yamada ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Neuronal Migration ◽  
Mitotic Cell ◽  
Cytoplasmic Dynein ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Microtubule Organization ◽  
Mitotic Entry ◽  
Binding Partner

ABSTRACT NDEL1 is a binding partner of LIS1 that participates in the regulation of cytoplasmic dynein function and microtubule organization during mitotic cell division and neuronal migration. NDEL1 preferentially localizes to the centrosome and is a likely target for cell cycle-activated kinases, including CDK1. In particular, NDEL1 phosphorylation by CDK1 facilitates katanin p60 recruitment to the centrosome and triggers microtubule remodeling. Here, we show that Aurora-A phosphorylates NDEL1 at Ser251 at the beginning of mitotic entry. Interestingly, NDEL1 phosphorylated by Aurora-A was rapidly downregulated thereafter by ubiquitination-mediated protein degradation. In addition, NDEL1 is required for centrosome targeting of TACC3 through the interaction with TACC3. The expression of Aurora-A phosphorylation-mimetic mutants of NDEL1 efficiently rescued the defects of centrosomal maturation and separation which are characteristic of Aurora-A-depleted cells. Our findings suggest that Aurora-A-mediated phosphorylation of NDEL1 is essential for centrosomal separation and centrosomal maturation and for mitotic entry.

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