scholarly journals Targeting Aurora A kinase activity with the investigational agent alisertib increases the efficacy of cytarabine through a FOXO-dependent mechanism

2012 ◽  
Vol 131 (11) ◽  
pp. 2693-2703 ◽  
Author(s):  
Kevin R. Kelly ◽  
Steffan T. Nawrocki ◽  
Claudia M. Espitia ◽  
Mengkun Zhang ◽  
Johnny J. Yang ◽  
...  
Keyword(s):  
Kinase Activity ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Investigational Agent ◽  
Dependent Mechanism

scholarly journals A Novel Cell-Based, High-Content Assay for Phosphorylation of Lats2 by Aurora A

2011 ◽  
Vol 16 (8) ◽  
pp. 925-931 ◽  
Author(s):  
Amy Emery ◽  
David A. Sorrell ◽  
Stacy Lawrence ◽  
Emma Easthope ◽  
Mark Stockdale ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Kinase Activity ◽  
High Content Screening ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Assay Performance ◽  
A Cell ◽  
Significant Addition ◽  
Specific Inhibitors

Aurora A kinase is a key regulator of mitosis, which is upregulated in several human cancers, making it a potential target for anticancer therapeutics. Consequently, robust medium- to high-throughput cell-based assays to measure Aurora A kinase activity are critical for the development of small-molecule inhibitors. Here the authors compare measurement of the phosphorylation of two Aurora A substrates previously used in high-content screening Aurora A assays, Aurora A itself and TACC3, with a novel substrate Lats2. Using antibodies directed against phosphorylated forms of Aurora A (pThr288), P-TACC3 (pSer558), and P-Lats2 (pSer83), the authors investigate their suitability in parallel for development of a cell-based assay using several reference Aurora inhibitors: MLN8054, VX680, and AZD1152-HQPA. They validate a combined assay of target-specific phosphorylation of Lats2 at the centrosome and an increase in mitotic index as a measure of Aurora A activity. The assay is both sensitive and robust and has acceptable assay performance for high-throughput screening or potency estimation from concentration–response assays. It has the advantage that it can be carried out using a commercially available monoclonal antibody against phospho-Lats2 and the widely available Cellomics ArrayScan HCS reader and thus represents a significant addition to the tools available for the identification of Aurora A specific inhibitors.

scholarly journals Aurora A kinase activity is required for localization of TACC3/ch-TOG/clathrin inter-microtubule bridges

2011 ◽  
Vol 4 (4) ◽  
pp. 409-412 ◽  
Author(s):  
Liam P. Cheeseman ◽  
Daniel G. Booth ◽  
Fiona E. Hood ◽  
Ian A. Prior ◽  
Stephen J. Royle
Keyword(s):  
Kinase Activity ◽  
Aurora A Kinase ◽  
Aurora A

scholarly journals Aurora A kinase activity is required to maintain an active spindle assembly checkpoint during prometaphase

2018 ◽  
Vol 131 (7) ◽  
pp. jcs191353 ◽  
Author(s):  
Thibault Courtheoux ◽  
Alghassimou Diallo ◽  
Arun Prasath Damodaran ◽  
David Reboutier ◽  
Erwan Watrin ◽  
...  
Keyword(s):  
Spindle Assembly Checkpoint ◽  
Kinase Activity ◽  
Spindle Assembly ◽  
Aurora A Kinase ◽  
Aurora A

Searching for Biomarkers of Aurora-A Kinase Activity:  Identification of in Vitro Substrates through a Modified KESTREL Approach

2005 ◽  
Vol 4 (4) ◽  
pp. 1296-1303 ◽  
Author(s):  
Sonia Troiani ◽  
Mauro Uggeri ◽  
Jürgen Moll ◽  
Antonella Isacchi ◽  
Henryk M. Kalisz ◽  
...  
Keyword(s):  
Kinase Activity ◽  
Aurora A Kinase ◽  
Aurora A

scholarly journals TPXL-1 activates Aurora A to clear contractile ring components from the polar cortex during cytokinesis

2018 ◽  
Vol 217 (3) ◽  
pp. 837-848 ◽  
Author(s):  
Sriyash Mangal ◽  
Jennifer Sacher ◽  
Taekyung Kim ◽  
Daniel Sampaio Osório ◽  
Fumio Motegi ◽  
...  
Keyword(s):  
Kinase Activity ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Active Process ◽  
Contractile Ring ◽  
Central Spindle ◽  
Inhibitory Signal ◽  
Molecular Identity ◽  
Anaphase Onset ◽  
Molecular Components

During cytokinesis, a signal from the central spindle that forms between the separating anaphase chromosomes promotes the accumulation of contractile ring components at the cell equator, while a signal from the centrosomal microtubule asters inhibits accumulation of contractile ring components at the cell poles. However, the molecular identity of the inhibitory signal has remained unknown. To identify molecular components of the aster-based inhibitory signal, we developed a means to monitor the removal of contractile ring proteins from the polar cortex after anaphase onset. Using this assay, we show that polar clearing is an active process that requires activation of Aurora A kinase by TPXL-1. TPXL-1 concentrates on astral microtubules coincident with polar clearing in anaphase, and its ability to recruit Aurora A and activate its kinase activity are essential for clearing. In summary, our data identify Aurora A kinase as an aster-based inhibitory signal that restricts contractile ring components to the cell equator during cytokinesis.

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 TPXL-1 Activates Aurora A to Clear Contractile Ring Components from the Polar Cortex During Cytokinesis

2017 ◽  
Author(s):  
Sriyash Mangal ◽  
Jennifer Sacher ◽  
Taekyung Kim ◽  
Daniel Sampaio Osório ◽  
Fumio Motegi ◽  
...  
Keyword(s):  
Kinase Activity ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Contractile Ring ◽  
Inhibitory Signal ◽  
Molecular Identity ◽  
Anaphase Onset ◽  
Cortical Contractility ◽  
Molecular Components ◽  
Insight Into

ABSTRACTDuring cytokinesis, a signal from the bundled microtubules that form between the separating anaphase chromosomes promotes the accumulation of contractile ring components at the cell equator, while a signal from the centrosomal microtubule asters inhibits accumulation of contractile ring components at the cell poles. However, the molecular identity of the inhibitory signal has remained unknown. To identify molecular components of the aster-based inhibitory signal, we developed a means to monitor the removal of contractile ring proteins from the polar cortex after anaphase onset. Using this assay, we show that polar clearing is an active process that requires activation of Aurora A kinase by TPXL-1. TPXL-1 concentrates on astral microtubules coincident with polar clearing in anaphase, and its ability to recruit Aurora A and activate its kinase activity are essential for clearing. In summary, our data identify Aurora A kinase as an aster-based inhibitory signal that restricts contractile ring components to the cell equator during cytokinesis.SUMMARYDuring cytokinesis, centrosomal asters inhibit cortical contractility at the cell poles. Mangal et al. provide molecular insight into this phenomenon, showing that TPXL-1, which localizes to astral microtubules, activates Aurora A kinase to clear contractile ring proteins from the polar cortex.

scholarly journals Caenorhabditis elegans Aurora A kinase is required for the formation of spindle microtubules in female meiosis

2015 ◽  
Vol 26 (23) ◽  
pp. 4187-4196 ◽  
Author(s):  
Eisuke Sumiyoshi ◽  
Yuma Fukata ◽  
Satoshi Namai ◽  
Asako Sugimoto
Keyword(s):  
Caenorhabditis Elegans ◽  
Kinase Activity ◽  
Active Form ◽  
Meiotic Spindle ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Female Meiosis ◽  
Germinal Vesicle Breakdown ◽  
Meiotic Spindles ◽  
Spindle Microtubules

In many animals, female meiotic spindles are assembled in the absence of centrosomes, the major microtubule (MT)-organizing centers. How MTs are formed and organized into meiotic spindles is poorly understood. Here we report that, in Caenorhabditis elegans, Aurora A kinase/AIR-1 is required for the formation of spindle microtubules during female meiosis. When AIR-1 was depleted or its kinase activity was inhibited in C. elegans oocytes, although MTs were formed around chromosomes at germinal vesicle breakdown (GVBD), they were decreased during meiotic prometaphase and failed to form a bipolar spindle, and chromosomes were not separated into two masses. Whereas AIR-1 protein was detected on and around meiotic spindles, its kinase-active form was concentrated on chromosomes at prometaphase and on interchromosomal MTs during late anaphase and telophase. We also found that AIR-1 is involved in the assembly of short, dynamic MTs in the meiotic cytoplasm, and these short MTs were actively incorporated into meiotic spindles. Collectively our results suggest that, after GVBD, the kinase activity of AIR-1 is continuously required for the assembly and/or stabilization of female meiotic spindle MTs.

scholarly journals Aurora A kinase activity influences calcium signaling in kidney cells

2011 ◽  
Vol 194 (1) ◽  
pp. 157-157
Author(s):  
Olga V. Plotnikova ◽  
Elena N. Pugacheva ◽  
Erica A. Golemis
Keyword(s):  
Calcium Signaling ◽  
Kinase Activity ◽  
Kidney Cells ◽  
Aurora A Kinase ◽  
Aurora A
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