iASPP contributes to cell cortex rigidity, mitotic cell rounding, and spindle positioning.
Amino Acid Motifs
HEK293 Cells
HeLa Cells
Humans
Intracellular Signaling Peptides and Proteins
/ chemistry
Microtubule-Associated Proteins
/ metabolism
Microtubules
/ metabolism
Mitosis
Myosin Type I
/ metabolism
Phosphoprotein Phosphatases
/ metabolism
Protein Binding
Repressor Proteins
/ chemistry
Spindle Apparatus
/ metabolism
Journal
The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356
Informations de publication
Date de publication:
06 12 2021
06 12 2021
Historique:
received:
01
12
2020
revised:
03
08
2021
accepted:
19
09
2021
entrez:
27
10
2021
pubmed:
28
10
2021
medline:
24
12
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34705028
pii: 212730
doi: 10.1083/jcb.202012002
pmc: PMC8562848
pii:
doi:
Substances chimiques
Intracellular Signaling Peptides and Proteins
0
MAPRE1 protein, human
0
Microtubule-Associated Proteins
0
PPP1R13L protein, human
0
Repressor Proteins
0
Phosphoprotein Phosphatases
EC 3.1.3.16
Myosin Type I
EC 3.6.1.-
MYO1C protein, human
EC 3.6.1.3
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2021 Mangon et al.
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