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13 results on '"Polverino, Federica"'

3. AMBRA1 phosphorylation by CDK1 and PLK1 regulates mitotic spindle orientation

Author

Faienza, Fiorella, Polverino, Federica, Rajendraprasad, Girish, Milletti, Giacomo, Hu, Zehan, Colella, Barbara, Gargano, Deborah, Strappazzon, Flavie, Rizza, Salvatore, Vistesen, Mette Vixø, Luo, Yonglun, Antonioli, Manuela, Cianfanelli, Valentina, Ferraina, Caterina, Fimia, Gian Maria, Filomeni, Giuseppe, De Zio, Daniela, Dengjel, Joern, Barisic, Marin, Guarguaglini, Giulia, Di Bartolomeo, Sabrina, and Cecconi, Francesco

Published
2023
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4. Contribution of AurkA/TPX2 Overexpression to Chromosomal Imbalances and Cancer.

Author

Polverino, Federica, Mastrangelo, Anna, and Guarguaglini, Giulia

Subjects
*CHROMOSOME segregation, *MICROTUBULE-associated proteins, *CELL division, *MICROTUBULES, *CHROMOSOMES
Abstract

The AurkA serine/threonine kinase is a key regulator of cell division controlling mitotic entry, centrosome maturation, and chromosome segregation. The microtubule-associated protein TPX2 controls spindle assembly and is the main AurkA regulator, contributing to AurkA activation, localisation, and stabilisation. Since their identification, AurkA and TPX2 have been described as being overexpressed in cancer, with a significant correlation with highly proliferative and aneuploid tumours. Despite the frequent occurrence of AurkA/TPX2 co-overexpression in cancer, the investigation of their involvement in tumorigenesis and cancer therapy resistance mostly arises from studies focusing only on one at the time. Here, we review the existing literature and discuss the mitotic phenotypes described under conditions of AurkA, TPX2, or AurkA/TPX2 overexpression, to build a picture that may help clarify their oncogenic potential through the induction of chromosome instability. We highlight the relevance of the AurkA/TPX2 complex as an oncogenic unit, based on which we discuss recent strategies under development that aim at disrupting the complex as a promising therapeutic perspective. [ABSTRACT FROM AUTHOR]

Published
2024
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5. AurkA nuclear localization is promoted by TPX2 and counteracted by protein degradation

Author

Asteriti, Italia Anna, primary, Polverino, Federica, additional, Stagni, Venturina, additional, Sterbini, Valentina, additional, Ascanelli, Camilla, additional, Naso, Francesco Davide, additional, Mastrangelo, Anna, additional, Rosa, Alessandro, additional, Paiardini, Alessandro, additional, Lindon, Catherine, additional, and Guarguaglini, Giulia, additional

Published
2023
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7. PHA-680626 Is an Effective Inhibitor of the Interaction between Aurora-A and N-Myc

Author

Boi, Dalila, primary, Souvalidou, Fani, additional, Capelli, Davide, additional, Polverino, Federica, additional, Marini, Grazia, additional, Montanari, Roberta, additional, Pochetti, Giorgio, additional, Tramonti, Angela, additional, Contestabile, Roberto, additional, Trisciuoglio, Daniela, additional, Carpinelli, Patrizia, additional, Ascanelli, Camilla, additional, Lindon, Catherine, additional, De Leo, Alessandro, additional, Saviano, Michele, additional, Di Santo, Roberto, additional, Costi, Roberta, additional, Guarguaglini, Giulia, additional, and Paiardini, Alessandro, additional

Published
2021
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8. Prdm16-mediated H3K9 methylation controls fibro-adipogenic progenitors identity during skeletal muscle repair

Author

Biferali, Beatrice, primary, Bianconi, Valeria, additional, Perez, Daniel Fernandez, additional, Kronawitter, Sophie Pöhle, additional, Marullo, Fabrizia, additional, Maggio, Roberta, additional, Santini, Tiziana, additional, Polverino, Federica, additional, Biagioni, Stefano, additional, Summa, Vincenzo, additional, Toniatti, Carlo, additional, Pasini, Diego, additional, Stricker, Sigmar, additional, Di Fabio, Romano, additional, Chiacchiera, Fulvio, additional, Peruzzi, Giovanna, additional, and Mozzetta, Chiara, additional

Published
2021
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9. A Focused Small-Molecule Screen Identifies PHA-680626 as an Amphosteric Inhibitor Disrupting the Interaction between Aurora-A and N-Myc

Author

Souvalidou, Fani, primary, Boi, Dalila, additional, Montanari, Roberta, additional, Polverino, Federica, additional, Marini, Grazia, additional, Capelli, Davide, additional, Pochetti, Giorgio, additional, Contestabile, Roberto, additional, Trisciuoglio, Daniela, additional, Tramonti, Angela, additional, Carpinelli, Patrizia, additional, Ascanelli, Camilla, additional, Lindon, Catherine, additional, De Leo, Alessandro, additional, Di Santo, Roberto, additional, Costi, Roberta, additional, Guarguaglini, Giulia, additional, and Paiardini, Alessandro, additional

Published
2021
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13. PHA-680626 Is an Effective Inhibitor of the Interaction between Aurora-A and N-Myc

Author

Dalila Boi, Fani Souvalidou, Davide Capelli, Federica Polverino, Grazia Marini, Roberta Montanari, Giorgio Pochetti, Angela Tramonti, Roberto Contestabile, Daniela Trisciuoglio, Patrizia Carpinelli, Camilla Ascanelli, Catherine Lindon, Alessandro De Leo, Michele Saviano, Roberto Di Santo, Roberta Costi, Giulia Guarguaglini, Alessandro Paiardini, Capelli, Davide [0000-0002-6716-3854], Polverino, Federica [0000-0002-0048-6122], Montanari, Roberta [0000-0002-7533-5425], Tramonti, Angela [0000-0002-5625-1170], Contestabile, Roberto [0000-0002-5235-9993], Trisciuoglio, Daniela [0000-0002-7007-7914], Lindon, Catherine [0000-0003-3554-2574], De Leo, Alessandro [0000-0001-5596-7217], Saviano, Michele [0000-0001-5086-2459], Di Santo, Roberto [0000-0002-4279-7666], Guarguaglini, Giulia [0000-0002-7541-8183], Paiardini, Alessandro [0000-0001-9078-7545], and Apollo - University of Cambridge Repository

Subjects
binding, QH301-705.5, kinase inhibitor, Protein Conformation, Drug Evaluation, Preclinical, Antineoplastic Agents, competitive, Aurora-A, Binding, Competitive, Catalysis, Article, Cell Line, Inorganic Chemistry, Neuroblastoma, Adenosine Triphosphate, drug evaluation, preclinical, Humans, Pyrroles, Biology (General), Physical and Theoretical Chemistry, Amphosteric inhibitors, N-Myc, neuroblastoma, PHA-680626, adenosine triphosphate, antineoplastic agents, Aurora Kinase A, azepines, benzazepines, binding sites, binding, competitive, cell line, drug evaluation, preclinical, humans, N-Myc proto-oncogene protein, protein conformation, protein kinase inhibitors, pyrazoles, pyrimidines, pyrroles, surface plasmon resonance, QD1-999, Molecular Biology, Protein Kinase Inhibitors, Spectroscopy, N-Myc Proto-Oncogene Protein, Binding Sites, Organic Chemistry, General Medicine, Azepines, amphosteric inhibitors, Benzazepines, Surface Plasmon Resonance, Computer Science Applications, Chemistry, Pyrimidines, Pyrazoles
Abstract

Neuroblastoma is a severe childhood disease, accounting for ~10% of all infant cancers. The amplification of the MYCN gene, coding for the N-Myc transcriptional factor, is an essential marker correlated with tumor progression and poor prognosis. In neuroblastoma cells, the mitotic kinase Aurora-A (AURKA), which is another protein frequently overexpressed in cancer, prevents N-Myc degradation, by directly binding to a highly conserved N-Myc region, i.e. Myc Box I. As a result, elevated levels of N-Myc, which are required for the growth of MYCN amplified cells, are observed. During the last years, it has been demonstrated that the ATP competitive inhibitors of AURKA CD532, MLN8054 and Alisertib also cause essential conformational changes in the structure of the activation loop of the kinase that prevent NMyc binding, thus impairing the formation of the AURKA /N-Myc complex. In this study, starting from a screening of crystal structures of AURKA in complex with known inhibitors, we identified additional compounds affecting the conformation of the kinase activation loop. We assessed the ability of such compounds to disrupt the interaction between AURKA and N-Myc in vitro, using Surface Plasmon Resonance competition assays, and in tumor cell lines overexpressing MYCN, by performing Proximity Ligation Assays. Finally, their effects on N-Myc cellular levels and cell viability were also investigated. Our results, identifying PHA-680626 as an amphosteric inhibitor both in vitro and MYCN overexpressing cell lines, expand the repertoire of known conformational disrupting inhibitors of the AURKA /N-Myc complex, and confirm that altering the conformation of the activation loop of AURKA with a small molecule is an effective strategy to destabilize the AURKA/N-Myc interaction in neuroblastoma cancer cells.

Published
2021

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