The AurkA kinase is a well-known mitotic regulator, frequently overexpressed in tumors. The microtubule-binding protein TPX2 controls AurkA activity, localization, and stability in mitosis. Non-mitotic roles of AurkA are emerging, and increased nuclear localization in interphase has been correlated with AurkA oncogenic potential. Still, the mechanisms leading to AurkA nuclear accumulation are poorly explored. Here, we investigated these mechanisms under physiological or overexpression conditions. We observed that AurkA nuclear localization is influenced by the cell cycle phase and nuclear export, but not by its kinase activity. Importantly, AURKA overexpression is not sufficient to determine its accumulation in interphase nuclei, which is instead obtained when AURKA and TPX2 are co-overexpressed or, to a higher extent, when proteasome activity is impaired. Expression analyses show that AURKA, TPX2, and the import regulator CSE1L are co-overexpressed in tumors. Finally, using MCF10A mammospheres we show that TPX2 co-overexpression drives protumorigenic processes downstream of nuclear AurkA. We propose that AURKA/TPX2 co-overexpression in cancer represents a key determinant of AurkA nuclear oncogenic functions.

AurkA nuclear localization is promoted by TPX2 and counteracted by protein degradation / Anna Asteriti, Italia; Polverino, Federica; Stagni, Venturina; Sterbini, Valentina; Ascanelli, Camilla; Davide Naso, Francesco; Mastrangelo, Anna; Rosa, Alessandro; Paiardini, Alessandro; Lindon, Catherine; Guarguaglini, Giulia. - In: LIFE SCIENCE ALLIANCE. - ISSN 2575-1077. - 6:5(2023). [10.26508/lsa.202201726]

AurkA nuclear localization is promoted by TPX2 and counteracted by protein degradation

Federica Polverino;Anna Mastrangelo;Alessandro Rosa;Alessandro Paiardini;Giulia Guarguaglini
2023

Abstract

The AurkA kinase is a well-known mitotic regulator, frequently overexpressed in tumors. The microtubule-binding protein TPX2 controls AurkA activity, localization, and stability in mitosis. Non-mitotic roles of AurkA are emerging, and increased nuclear localization in interphase has been correlated with AurkA oncogenic potential. Still, the mechanisms leading to AurkA nuclear accumulation are poorly explored. Here, we investigated these mechanisms under physiological or overexpression conditions. We observed that AurkA nuclear localization is influenced by the cell cycle phase and nuclear export, but not by its kinase activity. Importantly, AURKA overexpression is not sufficient to determine its accumulation in interphase nuclei, which is instead obtained when AURKA and TPX2 are co-overexpressed or, to a higher extent, when proteasome activity is impaired. Expression analyses show that AURKA, TPX2, and the import regulator CSE1L are co-overexpressed in tumors. Finally, using MCF10A mammospheres we show that TPX2 co-overexpression drives protumorigenic processes downstream of nuclear AurkA. We propose that AURKA/TPX2 co-overexpression in cancer represents a key determinant of AurkA nuclear oncogenic functions.
2023
AurkA; TPX2; mitosis
01 Pubblicazione su rivista::01a Articolo in rivista
AurkA nuclear localization is promoted by TPX2 and counteracted by protein degradation / Anna Asteriti, Italia; Polverino, Federica; Stagni, Venturina; Sterbini, Valentina; Ascanelli, Camilla; Davide Naso, Francesco; Mastrangelo, Anna; Rosa, Alessandro; Paiardini, Alessandro; Lindon, Catherine; Guarguaglini, Giulia. - In: LIFE SCIENCE ALLIANCE. - ISSN 2575-1077. - 6:5(2023). [10.26508/lsa.202201726]
File allegati a questo prodotto
File Dimensione Formato  
Asteriti_AurkA_2023.pdf

accesso aperto

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Creative commons
Dimensione 2.71 MB
Formato Adobe PDF
2.71 MB Adobe PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1670054
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 4
  • ???jsp.display-item.citation.isi??? 4
social impact