AurkA nuclear localization is promoted by TPX2 and counteracted by protein degradation.
Journal
Life science alliance
ISSN: 2575-1077
Titre abrégé: Life Sci Alliance
Pays: United States
ID NLM: 101728869
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
received:
16
09
2022
revised:
01
02
2023
accepted:
01
02
2023
entrez:
16
2
2023
pubmed:
17
2
2023
medline:
22
2
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 36797043
pii: 6/5/e202201726
doi: 10.26508/lsa.202201726
pmc: PMC9936162
pii:
doi:
Substances chimiques
Aurora Kinase A
EC 2.7.11.1
Cell Cycle Proteins
0
Microtubule-Associated Proteins
0
Nuclear Proteins
0
TPX2 protein, human
0
AURKA protein, human
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/R004137/1
Pays : United Kingdom
Informations de copyright
© 2023 Asteriti et al.
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