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.

scholarly journals MLN8054, an Inhibitor of Aurora A Kinase, Induces Senescence in Human Tumor Cells Both In vitro and In vivo

2010 ◽  
Vol 8 (3) ◽  
pp. 373-384 ◽  
Author(s):  
Jessica J. Huck ◽  
Mengkun Zhang ◽  
Alice McDonald ◽  
Doug Bowman ◽  
Kara M. Hoar ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Human Tumor ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Human Tumor Cells

scholarly journals ADR1-Mediated Transcriptional Activation Requires the Presence of an Intact TFIID Complex

1998 ◽  
Vol 18 (10) ◽  
pp. 5861-5867 ◽  
Author(s):  
Philip B. Komarnitsky ◽  
Edward R. Klebanow ◽  
P. Anthony Weil ◽  
Clyde L. Denis
Keyword(s):  
Transcriptional Activation ◽  
Yeast Cells ◽  
Binding Studies ◽  
Whole Cell ◽  
Transactivation Domains ◽  
Cell Extracts ◽  
Genes Expression ◽  
Tfiid Complex

ABSTRACT The yeast transcriptional activator ADR1, which is required forADH2 and other genes’ expression, contains four transactivation domains (TADs). While previous studies have shown that these TADs act through GCN5 and ADA2, and presumably TFIIB, other factors are likely to be involved in ADR1 function. In this study, we addressed the question of whether TFIID is also required for ADR1 action. In vitro binding studies indicated that TADI of ADR1 was able to retain TAFII90 from yeast extracts and TADII could retain TBP and TAFII130/145. TADIV, however, was capable of retaining multiple TAFIIs, suggesting that TADIV was binding TFIID from yeast whole-cell extracts. The ability of TADIV truncation derivatives to interact with TFIID correlated with their transcription activation potential in vivo. In addition, the ability of LexA-ADR1-TADIV to activate transcription in vivo was compromised by a mutation in TAFII130/145. ADR1 was found to associate in vivo with TFIID in that immunoprecipitation of either TAFII90 or TBP from yeast whole-cell extracts specifically coimmunoprecipitated ADR1. Most importantly, depletion of TAFII90 from yeast cells dramatically reducedADH2 derepression. These results indicate that ADR1 physically associates with TFIID and that its ability to activate transcription requires an intact TFIID complex.

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.

A Novel Small Molecule Inhibitor for Aurora-A Kinase Inhibits the Growth of Cervical Cancer In Vitro and In Vivo.

2010 ◽  
Vol 83 (Suppl_1) ◽  
pp. 344-344
Author(s):  
Patricia Y. Akinfenwa ◽  
Nonna V. Kolomeyevskaya ◽  
Claire M. Mach ◽  
Zhen Li ◽  
Matthew L. Anderson
Keyword(s):  
Cervical Cancer ◽  
Small Molecule ◽  
Small Molecule Inhibitor ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Molecule Inhibitor

scholarly journals Interaction of Aurora-A and centrosomin at the microtubule-nucleating site in Drosophila and mammalian cells

2003 ◽  
Vol 162 (5) ◽  
pp. 757-764 ◽  
Author(s):  
Yasuhiko Terada ◽  
Yumi Uetake ◽  
Ryoko Kuriyama
Keyword(s):  
Mammalian Cells ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Mitotic Spindles ◽  
Microtubule Nucleation ◽  
Microtubule Organization ◽  
Centrosomal Protein ◽  
Spindle Poles

A mitosis-specific Aurora-A kinase has been implicated in microtubule organization and spindle assembly in diverse organisms. However, exactly how Aurora-A controls the microtubule nucleation onto centrosomes is unknown. Here, we show that Aurora-A specifically binds to the COOH-terminal domain of a Drosophila centrosomal protein, centrosomin (CNN), which has been shown to be important for assembly of mitotic spindles and spindle poles. Aurora-A and CNN are mutually dependent for localization at spindle poles, which is required for proper targeting of γ-tubulin and other centrosomal components to the centrosome. The NH2-terminal half of CNN interacts with γ-tubulin, and induces cytoplasmic foci that can initiate microtubule nucleation in vivo and in vitro in both Drosophila and mammalian cells. These results suggest that Aurora-A regulates centrosome assembly by controlling the CNN's ability to targeting and/or anchoring γ-tubulin to the centrosome and organizing microtubule-nucleating sites via its interaction with the COOH-terminal sequence of CNN.

scholarly journals Adenovirus Protein VII Condenses DNA, Represses Transcription, and Associates with Transcriptional Activator E1A

2004 ◽  
Vol 78 (12) ◽  
pp. 6459-6468 ◽  
Author(s):  
Jeffrey S. Johnson ◽  
Yvonne N. Osheim ◽  
Yuming Xue ◽  
Margaux R. Emanuel ◽  
Peter W. Lewis ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Transcriptional Repression ◽  
Function Analysis ◽  
Specific Protein ◽  
In Vitro Translation ◽  
Major Protein ◽  
Lampbrush Chromosomes ◽  
Binding Studies

ABSTRACT Adenovirus protein VII is the major protein component of the viral nucleoprotein core. It is highly basic, and an estimated 1070 copies associate with each viral genome, forming a tightly condensed DNA-protein complex. We have investigated DNA condensation, transcriptional repression, and specific protein binding by protein VII. Xenopus oocytes were microinjected with mRNA encoding HA-tagged protein VII and prepared for visualization of lampbrush chromosomes. Immunostaining revealed that protein VII associated in a uniform manner across entire chromosomes. Furthermore, the chromosomes were significantly condensed and transcriptionally silenced, as judged by the dramatic disappearance of transcription loops characteristic of lampbrush chromosomes. During infection, the protein VII-DNA complex may be the initial substrate for transcriptional activation by cellular factors and the viral E1A protein. To investigate this possibility, mRNAs encoding E1A and protein VII were comicroinjected into Xenopus oocytes. Interestingly, whereas E1A did not associate with chromosomes in the absence of protein VII, expression of both proteins together resulted in significant association of E1A with lampbrush chromosomes. Binding studies with proteins produced in bacteria or human cells or by in vitro translation showed that E1A and protein VII can interact in vitro. Structure-function analysis revealed that an N-terminal region of E1A is responsible for binding to protein VII. These studies define the in vivo functions of protein VII in DNA binding, condensation, and transcriptional repression and indicate a role in E1A-mediated transcriptional activation of viral genes.

scholarly journals CEP55 promotes cilia disassembly through stabilizing Aurora A kinase

2021 ◽  
Vol 220 (2) ◽  
Author(s):  
Yu-Cheng Zhang ◽  
Yun-Feng Bai ◽  
Jin-Feng Yuan ◽  
Xiao-Lin Shen ◽  
Yu-Ling Xu ◽  
...  
Keyword(s):  
Cell Surface ◽  
Primary Cilia ◽  
Perinatal Death ◽  
Clinical Manifestations ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Mammalian Development ◽  
Polycystic Kidneys ◽  
And Control

Primary cilia protrude from the cell surface and have diverse roles during development and disease, which depends on the precise timing and control of cilia assembly and disassembly. Inactivation of assembly often causes cilia defects and underlies ciliopathy, while diseases caused by dysfunction in disassembly remain largely unknown. Here, we demonstrate that CEP55 functions as a cilia disassembly regulator to participate in ciliopathy. Cep55−/− mice display clinical manifestations of Meckel–Gruber syndrome, including perinatal death, polycystic kidneys, and abnormalities in the CNS. Interestingly, Cep55−/− mice exhibit an abnormal elongation of cilia on these tissues. Mechanistically, CEP55 promotes cilia disassembly by interacting with and stabilizing Aurora A kinase, which is achieved through facilitating the chaperonin CCT complex to Aurora A. In addition, CEP55 mutation in Meckel–Gruber syndrome causes the failure of cilia disassembly. Thus, our study establishes a cilia disassembly role for CEP55 in vivo, coupling defects in cilia disassembly to ciliopathy and further suggesting that proper cilia dynamics are critical for mammalian development.

scholarly journals Transforming acidic coiled-coil 3 and Aurora-A interact in human thyrocytes and their expression is deregulated in thyroid cancer tissues

2007 ◽  
Vol 14 (3) ◽  
pp. 827-837 ◽  
Author(s):  
Salvatore Ulisse ◽  
Enke Baldini ◽  
Matteo Toller ◽  
Jean-Guy Delcros ◽  
Aurélie Guého ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Thyroid Cancer ◽  
Coiled Coil ◽  
Human Thyroid ◽  
Mrna Levels ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Thyroid Cells ◽  
Cancer Tissues

Aurora-A kinase has recently been shown to be deregulated in thyroid cancer cells and tissues. Among the Aurora-A substrates identified, transforming acidic coiled-coil (TACC3), a member of the TACC family, plays an important role in cell cycle progression and alterations of its expression occur in different cancer tissues. In this study, we demonstrated the expression of the TACC3 gene in normal human thyroid cells (HTU5), and its modulation at both mRNA and protein levels during cell cycle. Its expression was found, with respect to HTU5 cells, unchanged in cells derived from a benign thyroid follicular tumor (HTU42), and significantly reduced in cell lines derived from follicular (FTC-133), papillary (B-CPAP), and anaplastic thyroid carcinomas (CAL-62 and 8305C). Moreover, in 16 differentiated thyroid cancer tissues, TACC3 mRNA levels were found, with respect to normal matched tissues, reduced by twofold in 56% of cases and increased by twofold in 44% of cases. In the same tissues, a correlation between the expression of the TACC3 and Aurora-A mRNAs was observed. TACC3 and Aurora-A interact in vivo in thyroid cells and both proteins localized onto the mitotic structure of thyroid cells. Finally, TACC3 localization on spindle microtubule was no more observed following the inhibition of Aurora kinase activity by VX-680. We propose that Aurora-A and TACC3 interaction is important to control the mitotic spindle organization required for proper chromosome segregation.

scholarly journals Aurora A kinase activation: Different means to different ends

2021 ◽  
Vol 220 (9) ◽  
Author(s):  
Nicolas Tavernier ◽  
Frank Sicheri ◽  
Lionel Pintard
Keyword(s):  
Spindle Assembly ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Serine Threonine Kinase ◽  
Kinase Activation ◽  
Mitotic Entry ◽  
Threonine Kinase ◽  
Molecular Studies ◽  
Signaling Events ◽  
Cellular Context

Aurora A is a serine/threonine kinase essential for mitotic entry and spindle assembly. Recent molecular studies have revealed the existence of multiple, distinct mechanisms of Aurora A activation, each occurring at specific subcellular locations, optimized for cellular context, and primed by signaling events including phosphorylation and oxidation.

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