iASPP contributes to cell cortex rigidity, mitotic cell rounding, and spindle positioning
| Autor: | Sabine Quitard, Mohamed Lala Bouali, Mira Kuzmić, Pascal Verdier-Pinard, Pierre-Henri Puech, Danièle Salaun, Daniel Isnardon, Stéphane Audebert, Ali Badache, Aurélie Mangon, Sylvie Thuault |
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| Přispěvatelé: | Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Adhésion et Inflammation (LAI), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Turing Center for Living Systems, ANR-16-CE11-0008,flexiplex,Fonctions émergentes d'un inhibiteur de p53: une organisation macromoléculaire flexible pour des fonctions biologiques distinctes(2016) |
| Rok vydání: | 2020 |
| Předmět: |
MESH: Myosin Type I
[SDV]Life Sciences [q-bio] Amino Acid Motifs Mitosis Spindle Apparatus Biology medicine.disease_cause Microtubules 03 medical and health sciences MESH: Amino Acid Motifs Myosin Type I 0302 clinical medicine Microtubule MESH: Intracellular Signaling Peptides and Proteins Cell cortex MESH: Phosphoprotein Phosphatases medicine Phosphoprotein Phosphatases MESH: Protein Binding Humans MESH: Spindle Apparatus Actin 030304 developmental biology 0303 health sciences Mutation Gene knockdown MESH: Humans MESH: Microtubules Intracellular Signaling Peptides and Proteins Cell Biology MESH: Mitosis Cell biology Spindle apparatus Repressor Proteins MESH: Microtubule-Associated Proteins HEK293 Cells MESH: Repressor Proteins MESH: HEK293 Cells Cancer cell MESH: HeLa Cells Microtubule-Associated Proteins 030217 neurology & neurosurgery HeLa Cells Protein Binding |
| Zdroj: | Journal of Cell Biology Journal of Cell Biology, 2021, 220 (12), ⟨10.1083/jcb.202012002⟩ |
| ISSN: | 1540-8140 0021-9525 |
| DOI: | 10.1083/jcb.202012002⟩ |
| Popis: | International audience; iASPP is a protein mostly known as an inhibitor of p53 pro-apoptotic activity and a predicted regulatory subunit of the PP1 phosphatase, which is often overexpressed in tumors. We report that iASPP associates with the microtubule plus-end binding protein EB1, a central regulator of microtubule dynamics, via an SxIP motif. iASPP silencing or mutation of the SxIP motif led to defective microtubule capture at the cortex of mitotic cells, leading to abnormal positioning of the mitotic spindle. These effects were recapitulated by the knockdown of the membrane-to-cortex linker Myosin-Ic (Myo1c), which we identified as a novel partner of iASPP. Moreover, iASPP or Myo1c knockdown cells failed to round up upon mitosis because of defective cortical stiffness. We propose that by increasing cortical rigidity, iASPP helps cancer cells maintain a spherical geometry suitable for proper mitotic spindle positioning and chromosome partitioning. |
| Databáze: | OpenAIRE |
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