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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Asteriti, Italia Anna  ORCID logo  https://orcid.org/0000-0002-6582-5500
Polverino, Federica 
Stagni, Venturina 
Sterbini, Valentina 

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.

Description

Funder: Regione Lazio; Grant(s): Progetti Gruppi di Ricerca 2020 ID: A0375-2020-36597


Funder: AstraZeneca


Funder: Associazione Italiana per la Ricerca sul Cancro; Grant(s): MFAG-2017 ID:20447, IG-2021 ID: 25648

Keywords

Humans, Aurora Kinase A, Cell Cycle Proteins, Proteolysis, Microtubule-Associated Proteins, Nuclear Proteins, Neoplasms

Journal Title

Life Sci Alliance

Conference Name

Journal ISSN

2575-1077
2575-1077

Volume Title

6

Publisher

Life Science Alliance, LLC
Sponsorship
Biotechnology and Biological Sciences Research Council (BB/R004137/1)