AURKA destruction is decoupled from its activity at mitotic exit but essential to suppress interphase activity
In: ISSN: 0021-9533, 2020
Online
academicJournal
Zugriff:
International audience ; Activity of AURKA is controlled through multiple mechanisms including phosphorylation, ubiquitin-mediated degradation, and allosteric interaction with TPX2. Activity peaks at mitosis before AURKA is degraded during and after mitotic exit in a process strictly dependent on APC/C coactivator FZR1. We used FZR1 knockout cells (FZR1KO) and a novel FRET-based AURKA biosensor to investigate how activity is regulated in absence of destruction. We found that AURKA activity in FZR1KO cells dropped at mitotic exit as rapidly as in parental cells, despite absence of destruction. Unexpectedly, TPX2 was degraded normally in FZR1KO cells. Overexpression of an N-terminal TPX2 fragment sufficient for AURKA binding, but not degraded at mitotic exit, caused delay in AURKA inactivation. We conclude that AURKA inactivation at mitotic exit is determined not by its own degradation but by degradation of TPX2 and therefore dependent on CDC20 rather than FZR1. The biosensor revealed that FZR1 instead suppresses AURKA activity in interphase and is critically required for assembly of the interphase mitochondrial network after mitosis.
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AURKA destruction is decoupled from its activity at mitotic exit but essential to suppress interphase activity
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Autor/in / Beteiligte Person: | Abdelbaki, Ahmed ; Akman, H. Begum ; Poteau, Marion ; Grant, Rhys ; Gavet, Olivier ; Guarguaglini, Giulia ; Lindon, Catherine ; Sorbonne Université - UFR Sciences de la vie (UFR 927 ) ; Sorbonne Université (SU) ; Centre National de la Recherche Scientifique (CNRS) ; Intégrité du génome et cancers (IGC) ; École Pratique des Hautes Études (EPHE) ; Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Institut Gustave Roussy (IGR)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS) ; Institut Gustave Roussy (IGR) |
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Zeitschrift: | ISSN: 0021-9533, 2020 |
Veröffentlichung: | HAL CCSD ; Company of Biologists, 2020 |
Medientyp: | academicJournal |
DOI: | 10.1242/jcs.243071 |
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