scholarly journals Constitutive regulation of mitochondrial morphology by Aurora A kinase depends on a predicted cryptic targeting sequence at the N-terminus

Open Biology ◽  
2018 ◽  
Vol 8 (6) ◽  
pp. 170272 ◽  
Author(s):  
Rhys Grant ◽  
Ahmed Abdelbaki ◽  
Alessia Bertoldi ◽  
Maria P. Gavilan ◽  
Jörg Mansfeld ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Mitochondrial Fraction ◽  
Mitochondrial Morphology ◽  
Aurora A Kinase ◽  
Mitochondrial Network ◽  
Aurora A ◽  
Mitochondrial Targeting ◽  
Cell Extracts ◽  
N Terminus ◽  
Different Levels

Aurora A kinase (AURKA) is a major regulator of mitosis and an important driver of cancer progression. The roles of AURKA outside of mitosis, and how these might contribute to cancer progression, are not well understood. Here, we show that a fraction of cytoplasmic AURKA is associated with mitochondria, co-fractionating in cell extracts and interacting with mitochondrial proteins by reciprocal co-immunoprecipitation. We have also found that the dynamics of the mitochondrial network are sensitive to AURKA inhibition, depletion or overexpression. This can account for the different mitochondrial morphologies observed in RPE-1 and U2OS cell lines, which show very different levels of expression of AURKA. We identify the mitochondrial fraction of AURKA as influencing mitochondrial morphology, because an N-terminally truncated version of the kinase that does not localize to mitochondria does not affect the mitochondrial network. We identify a cryptic mitochondrial targeting sequence in the AURKA N-terminus and discuss how alternative conformations of the protein may influence its cytoplasmic fate.

scholarly journals Regulation of mitochondrial dynamics by Aurora A kinase

2017 ◽  
Author(s):  
Rhys Grant ◽  
Ahmed Abdelbaki ◽  
Alessia Bertoldi ◽  
Maria P Gavilan ◽  
Jörg Mansfeld ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fraction ◽  
Mitochondrial Morphology ◽  
Aurora A Kinase ◽  
Mitochondrial Network ◽  
Aurora A ◽  
Mitochondrial Targeting ◽  
Cell Extracts ◽  
Different Levels

AbstractAurora A kinase (AURKA) is a major regulator of mitosis and an important driver of cancer progression. The roles of AURKA outside of mitosis, and how these might contribute to cancer progression, are not well understood. Here we show that a fraction of cytoplasmic AURKA is associated with mitochondria, co-fractionating in cell extracts and interacting with mitochondrial proteins by reciprocal co-immunoprecipitation. We have also found that the dynamics of the mitochondrial network are sensitive to AURKA inhibition, depletion or overexpression. This can account for the different mitochondrial morphologies observed in RPE1 and U2OS cell lines, which show very different levels of expression of AURKA. We identify the mitochondrial fraction of AURKA as influencing mitochondrial morphology, since an N-terminally truncated version of the kinase that does not localize to mitochondria does not affect the mitochondrial network. We identify a cryptic mitochondrial targeting sequence in the AURKA N-terminus and discuss how alternative conformations of the protein may influence its cytoplasmic fate.

scholarly journals Human TPX2 is required for targeting Aurora-A kinase to the spindle

2002 ◽  
Vol 158 (4) ◽  
pp. 617-623 ◽  
Author(s):  
Thomas A. Kufer ◽  
Herman H.W. Silljé ◽  
Roman Körner ◽  
Oliver J. Gruss ◽  
Patrick Meraldi ◽  
...  
Keyword(s):  
Catalytic Domain ◽  
Major Protein ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Binding Studies ◽  
Serine Threonine Kinase ◽  
Cell Extracts ◽  
Prominent Component ◽  
Spindle Apparatus

Aurora-A is a serine-threonine kinase implicated in the assembly and maintenance of the mitotic spindle. Here we show that human Aurora-A binds to TPX2, a prominent component of the spindle apparatus. TPX2 was identified by mass spectrometry as a major protein coimmunoprecipitating specifically with Aurora-A from mitotic HeLa cell extracts. Conversely, Aurora-A could be detected in TPX2 immunoprecipitates. This indicates that subpopulations of these two proteins undergo complex formation in vivo. Binding studies demonstrated that the NH2 terminus of TPX2 can directly interact with the COOH-terminal catalytic domain of Aurora-A. Although kinase activity was not required for this interaction, TPX2 was readily phosphorylated by Aurora-A. Upon siRNA-mediated elimination of TPX2 from cells, the association of Aurora-A with the spindle microtubules was abolished, although its association with spindle poles was unaffected. Conversely, depletion of Aurora-A by siRNA had no detectable influence on the localization of TPX2. We propose that human TPX2 is required for targeting Aurora-A kinase to the spindle apparatus. In turn, Aurora-A might regulate the function of TPX2 during spindle assembly.

Aurora A kinase interacts with and phosphorylates VHL protein

Biologia ◽  
2012 ◽  
Vol 67 (5) ◽  
Author(s):  
Imen Ferchichi ◽  
Yannick Arlot ◽  
Jean-Yves Cremet ◽  
Claude Prigent ◽  
Amel Benammar Elgaaied
Keyword(s):  
Mitotic Spindle ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Hek 293 ◽  
Von Hippel Lindau ◽  
Cell Extracts ◽  
Vhl Protein ◽  
The Stability

AbstractThe serine/threonin kinase Aurora A is an oncoprotein, whereas von Hippel-Lindau protein (pVHL) is a tumor suppressor protein. Both proteins have the same localization during mitosis: in the mitotic spindle and the centrosome. These two proteins also have common functions, such as the regulation of the cell cycle, the stability of the mitotic spindle and both intervene in the functioning of centrosomes. In this study we have analyzed the interaction between Aurora A and pVHL with immunoprecipitation and in vitro phosphorylation experiments. We have confirmed that the immunoprecipitation of pVHL from Hek 293 cell extracts were coupled with Aurora A. In addition, the interaction between the two proteins has been tested by analyzing the phosphorylation of pVHL in vitro by Aurora A. The results revealed that pVHL was phosphorylated by Aurora A. In conclusion, the study demonstrated that Aurora A interacts with and phosphorylates pVHL. Given the role of these two proteins in cell division as well as their status in cancer, this interaction requires further investigation.

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 mediated phosphorylation of LDHB promotes glycolysis and tumor progression by relieving the substrate-inhibition effect

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Aoxing Cheng ◽  
Peng Zhang ◽  
Bo Wang ◽  
Dongdong Yang ◽  
Xiaotao Duan ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Cancer Progression ◽  
Substrate Inhibition ◽  
Lactate Production ◽  
Metabolic Reprogramming ◽  
Glycolytic Flux ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Inhibition Effect ◽  
A Subunit

AbstractOverexpressed Aurora-A kinase promotes tumor growth through various pathways, but whether Aurora-A is also involved in metabolic reprogramming-mediated cancer progression remains unknown. Here, we report that Aurora-A directly interacts with and phosphorylates lactate dehydrogenase B (LDHB), a subunit of the tetrameric enzyme LDH that catalyzes the interconversion between pyruvate and lactate. Aurora-A-mediated phosphorylation of LDHB serine 162 significantly increases its activity in reducing pyruvate to lactate, which efficiently promotes NAD+ regeneration, glycolytic flux, lactate production and bio-synthesis with glycolytic intermediates. Mechanistically, LDHB serine 162 phosphorylation relieves its substrate inhibition effect by pyruvate, resulting in remarkable elevation in the conversions of pyruvate and NADH to lactate and NAD+. Blocking S162 phosphorylation by expression of a LDHB-S162A mutant inhibited glycolysis and tumor growth in cancer cells and xenograft models. This study uncovers a function of Aurora-A in glycolytic modulation and a mechanism through which LDHB directly contributes to the Warburg effect.

Centrosome Aurora A gradient ensures single polarity axis in C. elegans embryos

2020 ◽  
Vol 48 (3) ◽  
pp. 1243-1253 ◽  
Author(s):  
Sukriti Kapoor ◽  
Sachin Kotak
Keyword(s):  
Symmetry Breaking ◽  
Cell Fate ◽  
Cell Cortex ◽  
Axis Formation ◽  
Aurora A Kinase ◽  
Aurora A ◽  
C Elegans ◽  
Cell Embryo ◽  
Polarity Establishment

Cellular asymmetries are vital for generating cell fate diversity during development and in stem cells. In the newly fertilized Caenorhabditis elegans embryo, centrosomes are responsible for polarity establishment, i.e. anterior–posterior body axis formation. The signal for polarity originates from the centrosomes and is transmitted to the cell cortex, where it disassembles the actomyosin network. This event leads to symmetry breaking and the establishment of distinct domains of evolutionarily conserved PAR proteins. However, the identity of an essential component that localizes to the centrosomes and promotes symmetry breaking was unknown. Recent work has uncovered that the loss of Aurora A kinase (AIR-1 in C. elegans and hereafter referred to as Aurora A) in the one-cell embryo disrupts stereotypical actomyosin-based cortical flows that occur at the time of polarity establishment. This misregulation of actomyosin flow dynamics results in the occurrence of two polarity axes. Notably, the role of Aurora A in ensuring a single polarity axis is independent of its well-established function in centrosome maturation. The mechanism by which Aurora A directs symmetry breaking is likely through direct regulation of Rho-dependent contractility. In this mini-review, we will discuss the unconventional role of Aurora A kinase in polarity establishment in C. elegans embryos and propose a refined model of centrosome-dependent symmetry breaking.

Activation of Aurora A kinase through the FGF1/FGFR signaling axis sustains the stem cell characteristics of glioblastoma cells

2016 ◽  
Vol 344 (2) ◽  
pp. 153-166 ◽  
Author(s):  
Yi-Chao Hsu ◽  
Chien-Yu Kao ◽  
Yu-Fen Chung ◽  
Don-Ching Lee ◽  
Jen-Wei Liu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Glioblastoma Cells ◽  
Fgfr Signaling ◽  
Signaling Axis
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